DeltaEF1 promotes breast cancer cell proliferation through down-regulating p21 expression.
Although the zinc finger-homeodomain transcription factor deltaEF1 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 deltaEF1 in MDA-MB-231 cells significantly promoted cell proliferation by increasing the cell number in S phase of the cell cycle. In contrast, deltaEF1 knockdown by RNA interference exhibited an opposite effect, highlighting a potent role of deltaEF1 to promote G1-S transition of breast cancer cells. Moreover, we demonstrated that deltaEF1 down-regulated p21 and concurrently up-regulated the expressions of CDK2 and CDK4 during this process. Further, deltaEF1 inhibited p21 transcription by recruiting to the E(2) box element on the p21 promoter. Depletion of endogenous deltaEF1 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 deltaEF1 on cell proliferation through p21 regulation was supported by an inverse correlation of deltaEF1 and p21 expressions observed in both breast cancer cell lines and clinical tumor specimens. Taken together, these observations suggest a dual effect of deltaEF1 in promoting breast cancer cell proliferation, by differentially regulating the cell cycle regulatory proteins.
Hu
Fen
F
Medical College of Nankai University, Tianjin, China.
Wang
Chuan
C
Du
Jun
J
Sun
Wei
W
Yan
Jidong
J
Mi
Dong
D
Zhang
Jie
J
Qiao
Yuhuan
Y
Zhu
Tianhui
T
Yang
Shuang
S
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D044584:Carcinoma, Ductal / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division; D003001:Cloning, Molecular; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D000071799:Zinc Finger E-box-Binding Homeobox 1
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1