δEF1 Promotes Breast Cancer Cell Proliferation through Down-regulating p21 Expression

Fen Hu (1) , Chuan Wang (1) , Jun Du (1) , Wei Sun (1) , Jidong Yan (1) , Dong Mi (1) , Jie Zhang (1) , Yuhuan Qiao (1) , Tianhui Zhu (1) , Shuang Yang (1)

1 Medical College of Nankai University

Although the zinc finger-homeodomain transcription factor δEF1 is implied as a regulatory factor at the crossroad between proliferation and differentiation in carcinogenesis, its potential effect in the regulation of cell cycle progression has not been well elucidated. In our present study, we provide novel finding that, in breast cancer, the ectopic expression of δEF1 in MDA-MB-231 cells significantly promoted cell proliferation by increasing the cell number in S phase of the cell cycle. In contrast, δEF1 knockdown by RNA interference exhibited an opposite effect, highlighting a potent role of δEF1 to promote G1-S transition of breast cancer cells. Moreover, we demonstrated that δEF1 down-regulated p21 and concurrently up-regulated the expressions of CDK2 and CDK4 during this process. Further, δEF1 inhibited p21 transcription by recruiting to the E-box element on the p21 promoter. Depletion of endogenous δEF1 in MDA-MB-231 cells was sufficient to allow an inherent release of p21 expression, thus resulting in the cell cycle arrest. In addition, the stimulatory effect of δEF1 on cell proliferation through p21 regulation was supported by an inverse correlation of δEF1 and p21 expressions observed in both breast cancer cell lines and clinical tumor specimens. Taken together, these observations suggest a dual effect of δEF1 in promoting breast cancer cell proliferation, by differentially regulating the cell cycle regulatory proteins.

Mots clés: δEF1; p21; CDK; cell cycle; breast cancer proliferation

Fen Hu, Chuan Wang, Jun Du, Wei Sun, Jidong Yan, et al.. δEF1 Promotes Breast Cancer Cell Proliferation through Down-regulating p21 Expression. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2010, ⟨10.1016/j.bbadis.2009.12.002⟩. ⟨hal-00562950⟩