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.
Bollmann
Julia
J
Department of Obstetrics and Gynecology, University of Regensburg, Landshuter Street. 65, 93053 Regensburg, Germany.
Ortmann
Olaf
O
Treeck
Oliver
O
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C111850:THEMIS2 protein, human; D004958:Estradiol