The human platelet-derived growth factor (PDGF) is one of several known growth factors involved in the regulation of cell proliferation. PDGF is composed of two polypeptide chains. PDGF- 1 and PDGF-2. One or both of these chains can be found in a number of human tumor cells which also express the PDGF receptor. The deregulation of PDGF expression might confer a growth advantage to those cells by autocrine stimulation and contribute to the malignant phenotype. We have started to investigate which mechanisms regulate PDGF expression in tumor versus normal cells. In addition, we wanted to know how a high level of PDGF expression would affect normal diploid cells or the complete organism. We found that PDGF-1 differs in its expression pattern from PDGF-2. PDGF-2 expression is controlled at three different levels. The PDGF-2 promoter, which was identified and dissected into its different regulatory elements, is one target for control in normal and tumor cells: other levels of regulation are posttranscriptional and include inhibition of translation by secondary RNA structures. A high expression of PDGF-2 gave rise to polyclonal tumors in mice injected with a retrovirus containing the normal PDGF-2 gene. Experiments with transgenic mice have been initiated to introduce the human genes for PDGF-1 and -2 into the germ line and study effects of their overexpression.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005547-02
Application #
3916898
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code