RhoA and RhoC differentially modulate estrogen receptor α recruitment, transcriptional activities, and expression in breast cancer cells (MCF-7)

• Published in: Journal of cancer research and clinical oncology Vol. 139; no. 12; pp. 2079 - 2088
• Main Authors: Malissein, Emilie, Meunier, Elise, Lajoie-Mazenc, Isabelle, Médale-Giamarchi, Claire, Dalenc, Florence, Doisneau-Sixou, Sophie F.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2013; Springer
• Subjects: Antineoplastic agents; Biological and medical sciences; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer Research; Cell Line, Tumor; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Female; Gene Expression Regulation, Neoplastic - drug effects; Gynecology. Andrology. Obstetrics; Hematology; Humans; Internal Medicine; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Oncology; Original Paper; Pharmacology. Drug treatments; Protein Binding - drug effects; Protein Binding - genetics; Response Elements; rho GTP-Binding Proteins - antagonists & inhibitors; rho GTP-Binding Proteins - metabolism; rhoA GTP-Binding Protein - antagonists & inhibitors; rhoA GTP-Binding Protein - metabolism; rhoC GTP-Binding Protein; RNA, Small Interfering - pharmacology; Signal Transduction - drug effects; Signal Transduction - genetics; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; Tumors; Estrogen receptor alpha; Transcription; RhoC; Progesterone receptor; RhoA; Breast disease; Breast cancer; Malignant tumor; Gene expression; Biological activity; Recruitment; Mammary gland diseases; Estrogen receptor α; Established cell line; Tumor cell; Cancer; Hormonal receptor
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-013-1533-y

Purpose RhoA and RhoC are closely related, small GTPases that are clearly involved in breast cancer tumorigenesis. Nonetheless, their specific roles in the control of estrogen receptor alpha (ERα) activities have not been elucidated. Methods We used siRNA sequences to specifically down-regulate RhoA and RhoC expression in ERα-positive breast adenocarcinoma MCF-7 cells. We then analyzed the consequences of down-regulation on ERα expression, ERα recruitment to the promoters of four target genes, and the mRNA levels of those genes. Results We demonstrated that RhoA and RhoC clearly and similarly modulated ERα recruitment to the vitellogenin estrogen responsive element (ERE) present in a luciferase reporter gene and to the promoters of progesterone receptor (PR), cathepsin D , and pS2 genes. Besides, RhoA up-regulated the ERE-luciferase reporter gene activity and PR mRNA expression and tended to down-regulate cathepsin D and pS2 mRNA expression. Conversely, RhoC inhibition had no significant effect at the mRNA level. Furthermore, RhoA inhibition, and to a lesser extent RhoC inhibition, increased ERα expression. No alteration in ERα mRNA levels was observed, suggesting potential post-translational control. Conclusions Taken together, our results strongly suggest that RhoA and RhoC play different, but clear, roles in ERα signaling. These GTPases are definitely involved, along with RhoB, in ERα recruitment and, to some extent, ERα cofactor balance. We hypothesize a differential role of RhoA in breast cancer tumors that depend on hormone status.