title: Inhibition of proliferation of estrogen receptor‑positive MCF‑7 human breast cancer cells by tamoxifen through c‑Jun transcription factors.
abstract: Activator of protein 1 (AP-1) is a heterodimeric transcription factor composed of various members of the Jun and Fos families and binds to DNA at specific AP-1 binding sites. AP-1 transcriptional activity is increased by phosphorylation at serine residues in the c‑Jun component of AP-1. In the present study, the proliferation of MCF-7 breast cancer cells was found to be suppressed by tamoxifen (TAM)-activated c-Jun through the protein kinase C (PKC) pathway. The molecular mechanism by which c‑Jun activation induces antiproliferative signals in estrogen receptor (ER)-positive MCF-7 human breast cancer cells remains unknown. TAM inhibited the proliferation of ER-positive MCF-7 human breast cancer cells and ER-negative MDA-MB-435 human breast cancer cells and 48 h incubation with 10 µM TAM led to inhibition of 80% of proliferation. In addition, no significant difference in c-Jun mRNA and protein levels was detected in MCF-7 and MDA-MB-435 cells stimulated by TAM for 48 h. TAM treatment of MCF-7 cells activated the transcriptional activity of AP-1, which responds specifically to phorbol ester. To determine the role of c-Jun in the antiproliferation of MCF-7 cells stimulated by TAM, the inhibition rates of MCF‑7 cells were correlated with c‑Jun expression and stimulation of TAM. Results showed that the inhibition rate of TAM-stimulated MCF-7 cells was positively regulated by overexpression of c-Jun and negatively regulated by underexpression of c-Jun. Overall, these results indicate that the TAM-stimulated antiproliferation of MCF-7 cells is positively regulated by c-Jun through activation of the PKC pathway.
authors: Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R China.
authors: Yan
authors: Y
authors: Xu
authors: Shi-Tao
authors: ST
authors: Zou
authors: Ran
authors: R
authors: Zhu
authors: Wei
authors: W
authors: Li
authors: Chun-Wei
authors: CW
authors: Gu
authors: Shao-Hua
authors: SH
authors: Wei
authors: Jia-Ming
authors: JM
authors: Xie
authors: Hao-Rong
authors: HR
authors: Wu
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016758:Genes, jun / Q000235:genetics; D006801:Humans; D061986:MCF-7 Cells; D011493:Protein Kinase C / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D018808:Transcription Factor AP-1; D013629:Tamoxifen; D011493:Protein Kinase C