Recipient Organization
OHIO STATE UNIVERSITY - VET MED
1900 COFFEY ROAD, 127L VMAB
COLUMBUS,OH 43210
Performing Department
PATHOBIOLOGY
Non Technical Summary
Researchers are always looking for more insight into cancer. The studies will provide important new data on the function of PTHrP and TGF-beta in lung cancer in human patients.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
To investigate the regulation of extracellular calcium and the role of transforming growth factor-beta in parathyroid hormone-related (PTHrP) expression and secretion by cancers of the lung.
Project Methods
Investigate expression of PTHrP, TGF-beta1-3 and TGF-beta receptors (I and II) and measure serum ionized calcium and PTHrP concentrations and urine excretion of calcium and phosphorus in humans with lung cancer and in SCID/beige mice with primary human lung cancer xenografts. Investigate the regulation of PTHrP expression and secretion by transforming growth factor-beta1, TGF-beta2, and TGF-beta3 in lung carcinomas in vitro. Investigate the molecular regulation of PTHrP mRNA steady state levels, stability, and alternate splicing by TGF-beta in vitro using lung carcinoma explants and cell lines. Investigate the role of the Smad signal transduction in TGF-beta-mediated stimulation of PTHrP expression and hypercalcemia in vivo using knock-out mice with chemically-induced lung cancer and haploinsufficiency of Smads 2, 3, and 4, and in vitro using lung cancer cell lines transfected with dominant-negative Smads 2 and 3