Introduction of human chromosome 13 into retinoblastoma-negative metastatic human prostate cancer cells increases their sensitivity to growth inhibition by transforming growth factor-beta 1

Like many other carcinomas, prostate cancer develops resistance to inhibiti on by transforming growth factor (TGF)-beta 1 during oncogenesis, One propo sed mechanism of TGF-beta 1 action posits action of the retinoblastoma prot ein (pRb) to suppress c-myc transcription to inhibit cellular proliferation . A metastatic human prostate cancer cell line, DU145, has both nonfunction al pRb and markedly reduced sensitivity to TGF-beta 1 growth inhibition. Th e defective rb gene in DU145 cells was replaced by a normal rb allele by mi crocell fusion of chromosome 13, Two subclones, DU145-Cl-I and DU145-Cl-II, were studied in vitro to determine whether the pRb restoration increased s ensitivity to the inhibitory effects of TGF-beta 1, By reverse transcriptas e-polymerase chain reaction, increased sensitivity to the inhibitory effect s of TGF-beta 1, By reverse transcriptase-polymerase chain reaction, parent al DU145 cells had TGF-beta receptors of Type I and Type II. Introduction o f chromosome 13 reduced the growth rate and prolonged the G(1) phase compar ed with the parental DU145 cell line. Moreover, responsiveness to TGF-beta 1 growth inhibition was restored in a dose-dependent manner. Transcription of c-myc was not altered by TGF-beta 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 wa s introduced, unknown tumor suppressor genes, not only rb, may be responsib le for the restoration of TGF-beta 1 growth inhibition.