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

• Published in: Molecular and cellular biochemistry Vol. 380; no. 1-2; pp. 143 - 151
• Main Authors: Babu, R. L., Naveen Kumar, M., Patil, Rajeshwari H., Devaraju, K. S., Ramesh, Govindarajan T., Sharma, S. Chidananda
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-08-2013; Springer; Springer Nature B.V
• Subjects: Activator protein 1; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - physiology; Biochemistry; Biomedical and Life Sciences; Breast cancer; Cardiology; Cell cycle; Cell Cycle - genetics; Cell Cycle - physiology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - genetics; Cells; Cyclin D1 - genetics; Cyclin E - genetics; Development and progression; Dose-Response Relationship, Drug; Drugs; Estrogen; Estrogen Antagonists - pharmacology; Estrogens; Estrogens - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Humans; Life Sciences; MCF-7 Cells; Medical Biochemistry; Oncogene Proteins - genetics; Oncology; Phenols; Proteins; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - physiology; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - physiology; Receptors, Estrogen - genetics; Reverse Transcriptase Polymerase Chain Reaction; Tamoxifen; Tamoxifen - pharmacology; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - physiology; Tamoxifen; MTT; AP-1; MCF-7; Estrogen; qRT-PCR
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-013-1667-x

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 (E
2
) 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 E
2
found to increase the cell proliferation by more than 35 % and TMX an antiestrogen decreased by 29 % compared to control. The E
2
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. E
2
also found to induce cyclin D1 and cyclin E1 mRNA transcripts of cell cycle regulators while TMX significantly decreased compared to control. Further E
2
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.