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.

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

“…A previous study by the present authors proposed FosB as an important transcription factor in CRC patients with high COX-2 tumor tissue expression, since FosB was overexpressed in these patients, comparing with patients who exhibited low COX-2 expression (19). FosB is a member of the AP-1 complex, which has been linked to malignant transformation in several types of cancer, and its components, including FosB, have important roles on cell proliferation (among other functions), which suggests their involvement in cancer development (27)(28)(29)(30). In the present study, the role of FosB on the COX-2/PGE2 axis was investigated.…”

Halofuginone induces the apoptosis of breast cancer cells and inhibits migration via downregulation of matrix metalloproteinase-9

“…This leads to the increasing activity of proteins that can directly regulate c-jun or c-fos expression (35). On the other hand, the transcription factor NF-κB forms a family of inducible transcription factors that regulates numerous genes associated with inflammation, cancer development and tumor invasion.…”

Cadmium induces oxidative stress and apoptosis in lung epithelial cells

“…Cell viability, MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was carried out as per the protocol described earlier with slight modifications (Babu et al, 2013). The MTT assay involves the reduction of the soluble yellow dye (MTT) to an insoluble purple formazan salt.…”