Progress 01/01/99 to 09/30/04
Outputs
The interest in dietary components, such as vitamin D, in the prevention of cancer has recently increased as the importance of this compound in regulation of cell growth and death decisions has become recognized. Normal cells have tight regulatory mechanisms underlying growth control and appropriate stimulation of programmed cell death (PCD) or apoptosis. Cancer is characterized by unregulated growth of the cells which are also resistant to apoptosis. In order to develop recommendations for preventive or therapeutic measures, it is important to understand the regulatory mechanisms of both growth and apoptosis. C3H10T1/2 cells provides an excellent model for the process of multistage carcinogenesis in cells. We have demonstrated that the regulation of sphingolipid metabolism (i.e. the interconversion of the sphingolipid ceramide to sphingosine-1-phosphate) is critical for cell decisions. Accumulation of ceramide will promote cell death, but intracellular converstion of
ceramide to sphingosine-1-phosphate promotes cell survival. We have shown that ceramide and sphingosine-1-phosphate promote opposing signaling pathways of the mitogen activated protein kinase (MAPK) family, SAPK and ERK. However, it is the downregulation of SAPK by sphingosine-1-phosphate that leads to the inhibition of apoptosis. Therefore, it is the balance of the activity of the MAPKs that determines a cells fate. We have also shown the active metabolite of vitamin D, 1,25 dihydroxyvitamn D (1,25(OH)2D) inhibits apoptosis in normal cells, but not ones containing a mutated gene (ras) commonly found in cancers. We have investigated the underlying mechanism of these effects on apoptosis and why the cells containing the oncogene are resistant to 1,25(OH)2D. To understand the mechanism of the effects of nutrients on cell growth and apoptosis, cell signaling pathways that we have investigated include NFkB, vascular endothelial growth factors and the MAPKs. We have shown that the enzyme
phosphatidylinositol-3 kinase (PI3K) plays a role in the 1,25(OH)2D-mediated changes, including NFkB and vascular endothelial growth factors. Therefore, it is becoming increasing clear that, like many other receptor mediated processes, PI3K is critical for many of the cellular responses mediated by 1,25(OH)2D. 1,25(OH)2D reduces the growth of most, but not all prostate cancer cells. We are currently investigating the signaling pathways that mediate the resistance to 1,25(OH)2D-mediated cell growth arrest, and it appears that activation of the downstream target of PI3K, Akt, may play a role. We have also begun to investigate the upstream molecular mechanism by which 1,25(OH)2D induces PI3K activity. Our research has begun to identify how vitamin D regulates cell growth and death decisions at various stages of cancer progression and during a stroke.
Impacts
This year about 552,000 Americans are expected to die of cancer and stroke killed almost 160,000 persons in 1997 alone. These are the second and third leading cause of death in the US, respectively. The mortality rate for Indiana of 374 death/100,000 is very similar to the national rates in 1990-1994. Understanding how growth and death decisions by cells are regulated will lead to improved dietary recommendations to 1) prevent or cure cancers will lead to reduction in the death rate, and 2) potentially greatly reduce the consequences of strokes in Indiana residents.
Publications
- Levine M.J. and D. Teegarden. (2004) 1,25-dihydroxycholecalciferol increases expression of vascular endothelial growth factor in C3H10T1/2 mouse embryo fibroblasts. J Nutr. 134:2244-50.
- Adams L.S. and D. Teegarden. (2004) 1,25-dihydroxycholecalciferol inhibits apoptosis in C3H10T1/2 murine fibroblast cells through activation of nuclear factor k B. J Nutr, In press.
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Progress 10/01/03 to 09/30/04
Outputs
The interest in dietary components, such as vitamin D, in the prevention of cancer has recently increased as the importance of this compound in regulation of cell growth and death decisions has become recognized. Normal cells have tight regulatory mechanisms underlying growth control and appropriate stimulation of programmed cell death (PCD) or apoptosis. Cancer is characterized by unregulated growth of the cells which are also resistant to apoptosis. In order to develop recommendations for preventive or therapeutic measures, it is important to understand the regulatory mechanisms of both growth and apoptosis. C3H10T1/2 cells provides an excellent model for the process of multistage carcinogenesis in cells. We have shown the active metabolite of vitamin D, 1,25 dihydroxyvitamn D (1,25(OH)2D) inhibits apoptosis in normal cells, but not ones containing a mutated gene (ras) commonly found in cancers. We have investigated the underlying mechanism of these effects on
apoptosis and why the cells containing the oncogene are resistant to 1,25(OH)2D. To understand the mechanism of the effects of nutrients on cell growth and apoptosis, cell signaling pathways that are being investigated include NFkB, vascular endothelial growth factors and the MAPKs. We have shown that the enzyme phosphatidylinositol-3 kinase plays a role in the 1,25(OH)2D-mediated changes, and we are investigating how the regulation occurs. We are also extending this research to other models, including prostate and breast cancer cells. Our research has begun to identify how vitamin D regulates cell growth and death decisions at various stages of cancer progression and during a stroke.
Impacts
This year about 552,000 Americans are expected to die of cancer and stroke killed almost 160,000 persons in 1997 alone. These are the second and third leading cause of death in the US, respectively. The mortality rate for Indiana of 374 death/100,000 is very similar to the national rates in 1990-1994. Understanding how growth and death decisions by cells are regulated will lead to improved dietary recommendations to 1) prevent or cure cancers will lead to reduction in the death rate, and 2) potentially greatly reduce the consequences of strokes in Indiana residents.
Publications
- Stedman, L.A., K.O. Nickel, J. Andrade, S. S. Castillo, J. R. Burgess and D. Teegarden. 1,25-dihydroxyvitamin D inhibits vitamin E succinate-induced apoptosis in C3H10T1/2 cells but not Harvey ras-transfected cells. Nutr Canc 45:93-100, 2003.
- Castillo, S.S., D. Teegarden. Sphingosine-1-phosphate inhibition of apoptosis requires mitogen activated protein kinase phosphatase-1. J. Nutr. 133:27-35, 2003.
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Progress 10/01/01 to 09/30/02
Outputs
The interest in dietary components, such a sphingolipids and vitamin D, in the prevention of cancer has recently increased as the importance of these compounds in regulation of cell growth and death decisions has become recognized. Normal cells have tight regulatory mechanisms underlying growth control and appropriate stimulation of programmed cell death (PCD) or apoptosis. Cancer is characterized by unregulated growth of the cells which are also resistant to apoptosis. In order to develop recommendations for preventive or therapeutic measures, it is important to understand the regulatory mechanisms of both growth and apoptosis. C3H10T1/2 cells provides an excellent model for the process of multistage carcinogenesis in cells. We have shown that these cells are resistant to apoptosis mediated by a lipid found in cell membranes (ceramide). In addition, data from our laboratory demonstrate that the active metabolite of vitamin D, 1,25 dihydroxyvitamn D (1,25(OH)2D)
inhibits apoptosis in normal cells, but not ones containing a mutated gene (ras) commonly found in cancers. We have investigated the underlying mechanism of these effects on apoptosis and why the cells containing the oncogene are resistant to 1,25(OH)2D. To understand the mechanism of the effects of nutrients on cell growth and apoptosis, cell signaling pathways that are being investigated include NFkB, vascular endothelial growth factors and the MAPKs. Our research has begun to identify how nutrients such as vitamin D and a class of fats called sphingolipids regulate cell growth and death decisions at various stages of cancer progression and during a stroke.
Impacts
This year about 552,000 Americans are expected to die of cancer and stroke killed almost 160,000 persons in 1997 alone. These are the second and third leading cause of death in the US, respectively. The mortality rate for Indiana of 374 death/100,000 is very similar to the national rates in 1990-1994. Understanding how growth and death decisions by cells are regulated will lead to improved dietary recommendations to 1) prevent or cure cancers will lead to reduction in the death rate, and 2) potentially greatly reduce the consequences of strokes in Indiana residents.
Publications
- No publications reported this period
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Progress 10/01/00 to 09/30/01
Outputs
We have shown that a fibroblast cell line (C3H10T1/2) is resistant to ceramide induced apoptosis. C3H10T1/2 cells provides an excellent model for the process of multistage carcinogenesis in cells. Data from our laboratory demonstrate that C3H10T1/2 cells treated with ceramide inhibited growth but did not stimulate apoptosis. We are also utilizing breast cell line that is also a model for multistage carcinogenesis for several of these studies. Cells are treated with apoptotic stimulators, such as vitamin E succinate or ceramine, and with the nutritrients of interest, such as ceramide or the active form of vitamin D. Apoptosis and angiogenesis are the endpoints. To understand the mechanism of the effects of nutrients on cell growth and apoptosis, cell signaling pathways that are being investigated include NFkB, vascular endothelial growth factors and the MAPKs. Our research has begun to identify how nutrients such as vitamin D and a class of fats called sphingolipids
regulate cell growth and death decisions at various stages of cancer progression and during a stroke.
Impacts
This year about 552,000 Americans are expected to die of cancer and stroke killed almost 160,000 persons in 1997 alone. These are the second and third leading cause of death in the US, respectively. The mortality rate for Indiana of 374 death/100,000 is very similar to the national rates in 1990-1994. Understanding how growth and death decisions by cells are regulated will lead to improved dietary recommendations to 1) prevent or cure cancers will lead to reduction in the death rate, and 2) potentially greatly reduce the consequences of strokes in Indiana residents.
Publications
- No publications reported this period
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Progress 10/01/99 to 09/30/00
Outputs
The interest in dietary components, such a sphingolipids and vitamin D, in the prevention of cancer has recently increased as the importance of these compounds in regulation of cell growth and death decisions has become recognized. Normal cells have tight regulatory mechanisms underlying growth control and appropriate stimulation of programmed cell death (PCD) or apoptosis. Cancer is characterized by unregulated growth of the cells which are also resistant to apoptosis. In order to develop recommendations for preventive or therapeutic measures, it is important to understand the regulatory mechanisms of both growth and apoptosis. The sphingolipid ceramide is a potent mediator of apoptosis, acting through the stress activated protein kinase (SAPK) pathway. SAPK is a member of a family of kinases (mitogen activated protein kinases, MAPKs). Ceramide can be metabolized to sphingosine-1-phosphate (S1P). In contrast to ceramide, sphingosine metabolites are associated with an
increase in ERK (another member of the MAPK family), cell proliferation and can inhibit apoptosis. We have shown that a fibroblast cell line (C3H10T1/2) is resistant to ceramide-induced apoptosis. C3H10T1/2 cells provide an excellent model for multistage carcinogenesis in cells. Our results demonstrate that metabolism of ceramide to S1P is essential for the apoptotic resistance to ceramide of the C3H10T1/2 cells. In addition, we have shown that MAPK phosphatase (MKP), which down regulates both ERK and SAPK, is essential for S1P inhibition of apoptosis. The difference between those cells undergoing apoptosis or not was activation of ERK, followed by a more rapid down regulation of SAPK. The studies proposed in our laboratory will investigate the role and underlying mechanism of ceramide metabolism in preventing apoptosis in a model for multistage carcinogenesis. We have extended this work to investigate the effect of calcitriol, the form of active vitamin D, on inhibition of growth and
apoptosis. Calcitriol can stimulate the release of ceramide in cells, and regulating sphingolipid metabolism. We have shown that calcitriol can inhibit both growth and apoptosis in C3H10T1/2 cells, but not in cells tranfected with the ras oncogene, which represents the initiation phase of cancer. Thus vitamin D treatment may allow apoptotic stimulators, both endogenous and during cancer therapy, to kill cancer cells but not normal cells. We are currently investigating if this resistance to calcitriol in the ras-containing cells is due to the vitamin D receptor action, or to alterations in the sphingolipid metabolism. Future studies will investigate the resistance to ceramide-induced apoptosis in other stages of carcinogenesis. Understanding the mechanism of apoptotic resistance in cells will aid in improving dietary recommendations for sphingolipids in prevention of cancers.
Impacts
The role of nutrients in cancer prevention or therapy has become an important issue as it has become recognized that various dietary factors, including vitamin D and a class of fats termed sphingolipids, can regulate cell growth and death. Understanding the regulation of growth and apoptosis by nutrients in cells during multistage carcinogenesis will aid in improving dietary recommendations for vitamin D and sphingolipids in prevention of cancers
Publications
- Teegarden, D., Nickel, K. P.; Shi, L. (2000) Characterization of 25-hydroxyvitamin D binding protein from intestinal cells. Biochemistry Biophysical Research Communication 275:845-849.
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Progress 10/01/98 to 09/30/99
Outputs
The interest in dietary components, such as sphingolipids and vitamin D, in the prevention of cancer has recently increased as the importance of these compounds in regulation of cell growth and death decisions has become recognized. Normal cells have tight regulatory mechanisms underlying growth control and appropriate stimulation of programmed cell death (PCD) or apoptosis. Cancer is characterized by unregulated growth of the cells which are also resistant to apoptosis. In order to develop recommendations for preventive or therapeutic measures, it is important to understand the regulatory mechanisms of both growth and apoptosis. The sphingolipid ceramide is a potent mediator of apoptosis, acting through the stress activated protein kinase (SAPK) pathway . SAPK is a member of a family of kinases (mitogen activated protein kinases, MAPKs). Ceramide can be metabolized to sphingosine and sphingosine 1-phosphate. In contrast to ceramide, sphingosine metabolites are
associated with an increase in ERK (another member of the MAPK family), cell proliferation and can inhibit apoptosis. We have shown that a fibroblast cell line (C3H10T1/2) is resistant to ceramide induced apoptosis. C3H10T1/2 cells provides an excellent model for the process of multistage carcinogenesis in cells. Data from the our laboratory demonstrate that C3H10T1/2 cells treated with ceramide inhibited growth, but did not stimulate apoptosis. On the other hand, a non-metabolizable analogue of ceramide, ceramine, stimulated apoptosis in C3H10T1/2 cells. In addition, apoptosis stimulated by ceramine was inhibited by a ceramide metabolite, sphingosine-1-phosphate. These results suggest that metabolism of ceramide to sphinogsine metabolites is essential for the apoptotic resistance to ceramide of the C3H10T1/2 cells. In addition, we have shown that MAPK phosphatase (MKP), which down regulates both ERK and SAPK, is essential for sphingosine-1-phosphate inhibition of apoptosis. However,
SAPK activity is increased with ceramine treatment with or without sphingosine-1-phosphate within 4 hours. In contrast, cells treated with ceramine in conjunction with spingosine1-phosphate which do not undergo apoptosis have an increase in ERK activity within 4 hours. Thus the difference between those cells undergoing apoptosis or not was activation of ERK, not down regulation of SAPK as might be predicted by the essentiality of MKP. The studies proposed in our laboratory will investigate the role and underlying mechanism of ceramide metabolism in preventing apoptosis mediated by ceramine in a model for multistage carcinogenesis. Future studies will investigate the role of MKP and ERK activation in aphingosine-1-phosphate inhibition of apoptosis. Future studies will also investigate the resistance to ceramide induced apoptosis in other stages of carcinogenesis. Understanding the mechanism of apoptotic resistance in cells will aid in improving dietary recommendations for sphingolipids
in prevention of cancers.
Impacts
(N/A)
Publications
- Xu, X., J.R. Burgess, and D. Teegarden. (1997) Increased activity and expression of prostaglandin H synthase in ras-transfected cells. Cancer Lett.119:887-92.
- Teegarden, D., S.C. Meredith and Michael D. Sitrin. (1997) Isolation and characterization of a 25-hydroxyvitamin D binding protein from rat enterocyte cytosol. J. Nutr. Biochem. 8:195-200.
- Teegarden, D.; X. Xu, and J.R. Burgess. (1996) Reduced phospholipase A2 activity in ras-transfected C3H10T1/2 cells. Cancer Lett..107:59-64.
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Progress 10/01/97 to 09/30/98
Outputs
The interest in dietary components, such as sphingolipids and vitamin D, in the prevention of cancer has recently increased as the importance of these compounds in regulation of cell growth and death decisions has become recognized. Normal cells have tight regulatory mechanisms underlying growth control and appropriate stimulation of programmed cell death (PCD) or apoptosis. Cancer is a multifactorial process involving the stages of initiation and progression leading to unregulated growth of the cells which are also resistant to apoptosis. In order to develop recommendations for preventive or therapeutic measures, it is important to understand the regulatory mechanisms of both growth and apoptosis. Ideally, cancer preventive measures would not stimulate normal cells but would stimulate cancer-causing mutated cells to undergo apoptosis. The sphingolipid ceramide is a potent mediator of apoptosis, acting through the stress activated protein kinase (SAPK) pathway . SAPK
is a member of a family of kinases (mitogen activated protein kinases, MAPKs). Ceramide can be metabolized to sphingosine and sphingosine 1-phosphate by the enzymes ceramidase and sphingosine kinase, respectively. In contrast to ceramide, sphingosine metabolites are associated with an increase in ERK (another member of the SAPK family), cell proliferation and can inhibit apoptosis by an as yet unknown mechanism. In our laboratory, we have shown that a fibroblast cell line (C3H10T12) is resistant to ceramide induced apoptosis. Previous research on lipid signalling pathways by the principal investigator used C3H10T12 cells transfected with the Harvey-ras (H-ras) oncogene. C3H10T12 cells provides an excellent model for the process of multistage carcinogenesis in cells. Data from the our laboratory demonstrate that C3H10T12 cells treated with the calcitriol and the cell permeable C-2 ceramide analogue inhibited growth, but did not stimulate apoptosis. On the other hand, a
non-metabolizable analogue of ceramide, ceramine, stimulated apoptosis in C3H10T12 cells. In addition, apoptosis stimulated by ceramine was inhibited by a ceramide metabolite, sphingosine-1-phosphate. In addition, SAPK activity is increased within 30 minutes and downregulated by 6 hours following ceramine treatement. In contrast, cells treated with ceramine in conjunction with spingosine1-phosphate which do not undergo apoptosis have an increase in ERK activity within 30 minutes. These results suggest that metabolism of ceramide to sphinogsine metabolites is essential for the apoptotic resistance to ceramide of the C3H10T12 cells. The studies proposed in our laboratory will investigate the role and underlying mechanism of ceramide metabolism in preventing apoptosis mediated by ceramide in a model for multistage carcinogenesis. Future studies will investigate resistance to ceramide induced apoptosis in other stages of carcinogenesis. Understanding the mechanism of apoptotic resistance
in cells will aid in improving dietary recommendations for sphingolipids in prevention of cancers.
Impacts
(N/A)
Publications
- Yen, S.-L., Y.-C. Lin, J. R. Burgess, and D. Teegarden. (1999) Reduction in phospholipase A2 and increase in prostaglandin H synthase-1 in ras-transfected C3H10T1/2 cells. Submitted to Lipids.
- Castillo, S.S., D. Teegarden. (1999) Mechanisms of resistance to 1 ,25-dihydroxyvitamin D3 and ceramide induced apoptosis. Submitted to Journal of Nutrition.
- Xu, X., J.R. Burgess, and D. Teegarden. (1997) Increased activity and expression of prostaglandin H synthase in ras-transfected cells. Cancer Lett.119:887-92.
- Teegarden, D., S.C. Meredith and Michael D. Sitrin. (1997) Isolation and characterization of a 25-hydroxyvitamin D binding protein from rat enterocyte cytosol. J. Nutr. Biochem. 8:195-200.
- Teegarden, D.; X. Xu, and J.R. Burgess. (1996) Reduced phospholipase A2 activity in ras-transfected C3H10T1/2 cells. Cancer Lett..107:59-64.
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Progress 10/01/96 to 09/30/97
Outputs
The active metabolite of vitamin D, calcitriol, has been investigated as a cancer therapy. It has been shown to inhibit the growth of a wide variety of cancer cell types. Recent studies in our laboratory have shown that calcitriol inhibits cell growth of both control and ras-transfected C3H10T1/2 cells. This cell type is an excellent model for multistage carcinogenesis. We have also shown that calcitriol enhances apoptosis in the control, but not the ras-transfected cells. The activity of the enzyme phospholipase A2 (PLA2) has been implicated as a potential necessary element in apoptosis. PLA2 activity is reduced by 50% in ras-transfected cells and following calcitriol treatment is increased 25% and 10% in control and ras-transfected cells. Thus the activity of PLA2 is still significantly lower in the ras-transfected cells. In other cell types, calcitriol stimulates the release of the lipid second messanger, ceramide, however in C3H10T1/2 cells ceramide is not
released. In addition, cAMP, which has been shown in other cells to mediate the effects of calcitriol on cell growth, is not increased in the C3H10T1/2 cells following calcitriol treatment. Thus, the C3H10T1/2 cells respond to calcitriol in mediating decreased cell growth and apoptosis, effects important in a cancer therapy, but through an as yet unidentified pathway in the cell. In addition, we have purified and are currently attempting to sequence a unique vitamin D binding protein. Though many of the effects of calcitriol are mediated through a classic vitamin D receptor, there are well documented effects that are independent of this receptor. The protein responsible for these receptor independent effects is as yet unknown. We are investigating the role of our unique protein in calcitriol signalling in cells, and hypothesize that it may be the other receptor. These studies will help to understand how calcitriol acts in cells and during inhibition of cell growth and apoptosis.
Understanding the mechanism of calcitriol will aid in designing treatments and preventive strategies for cancer.
Impacts
(N/A)
Publications
- Teegarden D, Meredith SC, Sitrin MD. Isolation and characterization of a 25-hydroxyvitamin D binding protein from rat enterocyte cytosol. J Nutr 8:195-200, 1997.
- Xu X, Burgess JR, Teegarden D. Increased prostaglandin H synthase-1 expression and activity level in stably Harvey-ras transfected C3H10T1/2 cells. Canc Lett 119:87-92, 1997.
- Teegarden D, Xu X, Burgess JR. Transfection of C3H10T1/2 cells with the harbey-ras oncogene reduces cytosolic phospholipase A2 function. Canc Lett. 107:59-64, 1996.
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Progress 10/01/95 to 09/30/96
Outputs
The activity of PLA2 assessed in an in vitro assay was lower in the ras-transfected compared to control C3H10T1/2 cells. The amount of PLA2 protein, assessed by Western blot analyses, was also lower in the ras-transfected compared to control cells. The activity of PGH synthase was higher in an in vitro assay in the ras-transfected C3H10T1/2 cells compared to control cells. The amount of PGH synthase-1 protein and PGH synthase-1 RNA was higher in the ras-transfected cells compared to control. The amount of PGH synthase-2 protein and RNA was similar in the two cell types. Cells in which the ras oncogene is under the control of an inducible promoter were used to determine the short term effects on PLA2 and PGH synthase following the expression of the ras oncogene. PLA2 activity and protein levels were reduced within 24 hours following expression of the activated ras gene in C3H10T1/2 cells, with a further reduction at 48 hours. On the other hand, PGH synthase protein and
mRNA levels were unchanged following 48 hours of activated ras gene expression. In addition, experiments were completed to assess the effect of vitamin D on the growth patterns of C3H10T1/2 cells in normal cells and cells which express the ras oncogene. C3H10T1/2 cell and activated ras gene containing cells were treated with calcitriol, the active metabolite of vitamin D.
Impacts
(N/A)
Publications
- Xu, X., D. Teegarden, J.R. Burgess. PLA2 activity in stably H-ras transformed C3H10T1/2 cells. (abstr) Experimental Biology, 1995.
- Teegarden, D., X. Xu, J.R. Burgess. Increased prostaglandin H synthase activity in H-ras-transfected cells (abstr) Experimental Biology, 1996.
- Teegarden, D., X. Xu, J.R. Burgess. Reduced phospholipase A2 activity in Harvey ras-transfected cells. Cancer Letters, 107:59-64, 1996.
- Teegarden, D., S.C. Meredith, M.D. Sitrin. Purification and characterization of 25-hydroxyvitamin D binding protein in rat enterocyte cytosol. Journal of Nutritional Biochemistry, In press.
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Progress 10/01/94 to 09/30/95
Outputs
The activity of the enzyme, phospholipase A2 (PLA2), was assessed in ras-transfected C3H10T1/2 cells. The activity of PLA2 assessed in an in vitro assay was lower in the ras-transfected compared to control, untransfected, C3H10T1/2 cells. The amount of PLA2 protein, assessed by Western blot analyses, was also lower in the ras-transfected compared to control cells. The activity of PGH synthase was higher in an invitro assay in the ras-transfected C3H10T1/2 cells compared to control cells. The amount of PGH synthase-1 protein and PGH synthase-1 RNA was higher in the ras-transfected cells compared to control. The amount of PGH synthase-2 protein and RNA was similar in the two cell types. Also, experiments were completed to assess the effect of fatty acids on the growth patterns (transformation) of C3H10T1/2 cells which express the ras oncogene. Cells in which the ras oncogene is under the control of an inducible promoter were pretreated for varying lengths of time with
fatty acid and then zinc added to induce the expression of the ras protein. Treatment with rachidonic acid at high levels (120uM) for 5 days inhibited transformation of the cells following the induction of the ras oncogene at 8 days. Transformation is further inhibited if the medium is replaced with medium containing 60 uM arachidonic acid compared to medium without any additional fatty acids for the last 3 days prior to induction of the ras oncogene. These data suggest a role of PLA2 and PGH synthase in patterns of cell growth in r.
Impacts
(N/A)
Publications
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