Autonomous Growth of Androgen-independent Human Prostatic Carcinoma Cells:Role of Transforming Growth Factor a

The androgen-independent prostatic carcinoma cell line PC3 is knownto exhibit autonomous growth in vitro and in vivo. The purpose of thepresent study was to investigate the role of transforming growth factor α (TGF-α) and its receptor, the epidermal growth factor (EGF) receptor,in the regulation of PC3 cell proliferation. Results showed that PC3 cellssecrete factors into conditioned medium that are mitogenic for the lessaggressive prostatic carcinoma lines DU 145 and LNCaP. Gel filtrationChromatograph) of PCS-conditioned medium revealed a major peak ofmitogenic activity at a molecular weight of 5,000 to 10,000 which wasinhibited by the addition of antibody to TGF-α. The synthesis andsecretion of TGF-α by PC3 cells were further demonstrated by imiminoblottingand radioimmunoassay. Radioreceptor analysis showed a single class (K4 5.3 nM) of EGF receptors on PC3 cells. The presence of Mr 170,000 EGF receptors on PC3 cells was further demonstrated byimmunoprecipitation of metabolically labeled proteins. TGF-α was effective in stimulating the growth of low-density, but not high-density, PC3cultures. In addition, the proliferation of PC3 cells under serumfreedefined conditions was inhibited by antibodies to TGF-α and/or the EGFreceptor. These data indicate that TGF-β/EGF receptor interactions arepartially responsible for autonomous growth of the PC3 cell line and mayexplain one mechanism of escape from androgen-dependent growth inhuman prostatic carcinoma.