ROLE OF PDGF EXPRESSSION IN THE NEOPLASTIC PROCESS

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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.