PMID- 17400812 OWN - NLM STAT- MEDLINE DCOM- 20070521 LR - 20161124 IS - 0022-0795 (Print) IS - 0022-0795 (Linking) VI - 193 IP - 1 DP - 2007 Apr TI - Coactivator-mediated estrogen response in human squamous cell carcinoma lines. PG - 147-55 AB - Steroid hormones such as 17beta-estradiol (E2) are critical to diverse cellular processes including tumorigenesis. A number of cofactors such as nuclear receptor corepressor (NCoR), CREB-binding protein (CBP), and steroid receptor coactivator 1 (SRC-1) interact with estrogen receptors (ERs) to regulate transcriptional repression or activation of target genes. Estrogen signaling in non-reproductive tract tissues such as skin is less well characterized and the effectiveness of anti-estrogen therapy for cancer arising from these tissues is unknown. We show that tamoxifen (TAM) treatment inhibited cell cycle progression and proliferation of human cancer lines derived from stratified squamous epithelium squamous cell carcinoma (SCC). E2 had no effect on proliferation of these lines despite low levels of ERalpha expression. The E2 treatment promoted displacement of the NCoR from ERalpha and recruitment of CBP to the receptor. SRC-1 expression was not detected in these SCC lines; however, transient transfection of SRC-1, CBP, or both coactivators enhanced transactivation of an estrogen responsive promoter in cancer cells treated with E2 or TAM. In stable clones expressing SRC-1, the coactivator was recruited to ERalpha along with CBP in E2 but not in TAM-treated cells. SRC-1 expression restored the E2-mediated proliferative response to human SCC lines. This increased proliferation correlated with increased extracellular signal regulated kinase 1 (ERK1) expression. SRC-1 and CBP were recruited to the proximal ERK1 promoter region in E2 but not in TAM-treated cells. We concluded that SRC-1 was a key molecular determinant of estrogen-mediated proliferation in human SCC lines. FAU - Ku, Tony K S AU - Ku TK AD - University of Illinois Cancer Center, Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina Street, Chicago, Illinois 60612, USA. FAU - Crowe, David L AU - Crowe DL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 0 (Estrogen Antagonists) RN - 0 (Estrogen Receptor alpha) RN - 0 (Estrogens) RN - 0 (Lipids) RN - 0 (Lipofectamine) RN - 0 (Transcription Factors) RN - 094ZI81Y45 (Tamoxifen) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (CREBBP protein, human) RN - EC 2.3.1.48 (Histone Acetyltransferases) RN - EC 2.3.1.48 (NCOA1 protein, human) RN - EC 2.3.1.48 (Nuclear Receptor Coactivator 1) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Blotting, Western/methods MH - Breast Neoplasms MH - CREB-Binding Protein/genetics/metabolism MH - Carcinoma, Squamous Cell/*metabolism MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Chromatin Immunoprecipitation MH - Estrogen Antagonists/*pharmacology MH - Estrogen Receptor alpha/*metabolism MH - Estrogens/*pharmacology MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Histone Acetyltransferases/genetics/*metabolism MH - Humans MH - Lipids/administration & dosage/genetics MH - Nuclear Receptor Coactivator 1 MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tamoxifen/*pharmacology MH - Transcription Factors/genetics/*metabolism MH - Transfection/methods EDAT- 2007/04/03 09:00 MHDA- 2007/05/22 09:00 CRDT- 2007/04/03 09:00 PHST- 2007/04/03 09:00 [pubmed] PHST- 2007/05/22 09:00 [medline] PHST- 2007/04/03 09:00 [entrez] AID - 193/1/147 [pii] AID - 10.1677/JOE-06-0029 [doi] PST - ppublish SO - J Endocrinol. 2007 Apr;193(1):147-55. doi: 10.1677/JOE-06-0029.