Estradici Activation of Human Colon Carcinoma-derived Caco-2 Cell Growth1

This is the first report on estrogen-dependent growth of human-derived colon carcinoma cells. Under selected conditions, growth of suhconfluent Caco-2 cells is triggered by estradiol. Cell growth is estradiol concentra tion dependent, with maximal effect occurring ut uhout 0.4 n\i. ( i row lit is prevented by two différentantiestrogens: the partial agonist, OH-Tamoxifen, and the pure antagonist. ICI 182,780. The growth effect is specific for estradiol since other hormonal steroids tested do not affect cell growth. The amount of estradiol receptor in subconfluent Caco-2 cells, detected by blot with monoclonal antibodies directed against the receptor as well as estradiol binding assays, is similar to that of the classical estradiolresponsive. human mammary cancer-derived MCF-7 cells. I :•,[ nidÃ-oltreatment of subcontinent Caco-2 cells rapidly and reversibly stimulates four important intermediates in a signal transduction pathway that is known to trigger cell proliferation: two members of the large family of c-src-related tyrosine kinases, c-src and c-yes; and two serine/threonine kinases, the mitogen-activated protein (MAP) kinases, erk-1 and erk-2. Tyrosine kinases activated by estradiol are up-stream MAP kinases and Caco-2 cell proliferation. In fact, genistein, a specific tyrosine kinase inhibitor, abolishes the estradiol stimulatory effect on both erk-2 activity and cell proliferation. Our findings show that in subconfluent Caco-2 cells, the estradiol-receptor complex activates the c-src, c-yes/MAP kinase path way and activates growth. This could have important implications for the understanding of human intestinal carcinogenesis.