Expression of differentiation-associated gene icb-1 is estrogen-responsive in ovarian and breast cancer cell lines.

icb-1 (C1orf38) is a human gene initially described by our group to be upregulated during in vitro differentiation processes of endometrial adenocarcinoma and leukemia cells triggered by different stimuli. We now report presence of a putative imperfect estrogen response element (ERE) in the promoter of icb-1 gene. Given that estrogens are known to regulate cellular differentiation processes of hormone-dependent tissues, we studied whether expression of icb-1 would be regulated by 17-beta (beta) estradiol in breast and ovarian cancer cells. As examined by means of real time PCR, treatment with 17-beta estradiol for at least 24h resulted in a significant increase of icb-1 transcript levels in ERalpha-positive MCF-7 breast cancer and OVCAR-3 ovarian cancer cells, but not in ERalpha-negative SK-BR-3 and SK-OV-3 cells. Upregulation of icb-1 transcript levels was also observed after treatment with specific ERalpha-agonist PPT and was inhibited by co-treatment with pure antiestrogen ICI 182,780 in MCF-7 and OVCAR-3 ovarian cancer cells. Treatment with cycloheximide totally inhibited estrogen effects suggesting that activation of icb-1 gene expression is no ERE-dependent early response but a secondary event requiring protein synthesis. The results of this study demonstrate that transcript levels of differentiation-associated gene icb-1 are estrogen-responsive in breast and ovarian cancer cells in an ERalpha-dependent manner. Whether icb-1 is a mediator of estrogen-triggered cellular differentiation processes has to be determined in further studies.