Introduction of Human Chromosome 13 into Retinoblastoma-Negative Metastatic Human Prostate Cancer Cells Increases Their Sensitivity to Growth Inhibition by Transforming Growth Factor-&be;1.
Like many other carcinomas, prostate cancer develops resistance to inhibition by transforming growth factor (TGF)-&be;1 during oncogenesis. One proposed mechanism of TGF-&be;1 action posits action of the retinoblastoma protein (pRb) to suppress c-myc transcription to inhibit cellular proliferation. A metastatic human prostate cancer cell line, DU145, has both nonfunctional pRb and markedly reduced sensitivity to TGF-&be;1 growth inhibition. The defective rb gene in DU145 cells was replaced by a normal rb allele by microcell fusion of chromosome 13. Two subclones, DU145-Cl-I and DU145-Cl-II, were studied in vitro to determine whether the pRb restoration increased sensitivity to the inhibitory effects of TGF-&be;1. By reverse transcriptase-polymerase chain reaction, increased sensitivity to the inhibitory effects of TGF-&BE;1. By reverse transcriptase-polymerase chain reaction, parental DU145 cells had TGF-b receptors of Type I and Type II. Introduction of chromosome 13 reduced the growth rate and prolonged the G1 phase compared with the parental DU145 cell line. Moreover, responsiveness to TGF-&be;1 growth inhibition was restored in a dose-dependent manner. Transcription of c-myc was not altered by TGF-&be;1 growth inhibition. Thus, DU145 cells presumably required the presence of wildtype rb to become growth inhibited that is independent of c-myc transcription. As the entire chromosome 13 was introduced, unknown tumor suppressor genes, not only rb, may be responsible for the restoration of TGF-&be;1 growth inhibition.
Steiner
MS
University of Tennessee Urologic Research Laboratories, Memphis, Tennessee.
Anthony
CT