title: Effect of estrogen and tamoxifen on the expression pattern of AP-1 factors in MCF-7 cells: role of c-Jun, c-Fos, and Fra-1 in cell cycle regulation.
abstract: The activated transcription factor ERα plays an important role in the breast development and progression of cancer. In a non-classical pathway ER interacts with other transcription factors AP-1, NFkB, SP1, etc. AP-1 transcription factors control rapid responses of mammalian cells to stimuli that impact proliferation, differentiation, and transformation. AP-1 factors are leucine zipper proteins belonging to members of the Jun family (c-Jun, JunB, and JunD) and Fos family (c-Fos, FosB, Fra-1, and Fra-2) proteins. Although AP-1 factors are well characterized, not much is known about the expression pattern of the AP-1 factors in breast cancer cells. Hence to determine which AP-1 factors are expressed and regulated by estrogen, we used human breast cancer MCF-7 cells as in vitro model system. The MCF-7 cells were treated with or without estradiol-17β (E2) or antiestrogen tamoxifen (TMX) and the cell proliferation and viability was assessed by MTT assay. The expression of different AP-1 factors was analyzed by semi-quantitative RT-PCR. The cells treated with E2 found to increase the cell proliferation by more than 35 % and TMX an antiestrogen decreased by 29 % compared to control. The E2 found to induce the expression of c-Jun, Fra-1, and c-Fos, while TMX decreased the expression. In addition TMX also decreased the mRNA levels of Jun-D and Fra-2. These results suggest that the AP-1 factors c-Jun, c-Fos, and Fra-1 may be involved in the proliferation and transformation of MCF-7 cells. E2 also found to induce cyclin D1 and cyclin E1 mRNA transcripts of cell cycle regulators while TMX significantly decreased compared to control. Further E2 induced the anti-apoptotic Bcl-2 and TMX decreased mRNA transcripts. The data presented here support the E2-ERα-mediated MCF-7 cell proliferation and confirms the role of AP-1 factors in cell cycle regulation.
authors.affiliation: Department of Microbiology and Biotechnology, Bangalore University, Bangalore, 560 056 Karnataka, India.
authors.forename: R L
authors.initials: RL
authors.lastname: Babu
authors.forename: M
authors.initials: M
authors.lastname: Naveen Kumar
authors.forename: Rajeshwari H
authors.initials: RH
authors.lastname: Patil
authors.forename: K S
authors.initials: KS
authors.lastname: Devaraju
authors.forename: Govindarajan T
authors.initials: GT
authors.lastname: Ramesh
authors.forename: S Chidananda
authors.initials: SC
authors.lastname: Sharma
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D019927:Cyclin E / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells; D015513:Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000502:physiology; D000099169:Fos-Related Antigen 1
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D019938:Cyclin D1; D019927:Cyclin E; D004965:Estrogen Antagonists; D004967:Estrogens; D015513:Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011960:Receptors, Estrogen; D013629:Tamoxifen; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1; C475820:CCNE1 protein, human