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001-es BibID:	BIBFORM061450
Első szerző:	Shen, Qiang
Cím:	The AP-1 transcription factor regulates breast cancer cell growth via cyclins and E2F factors / Q. Shen, I. P. Uray, Y. Li, T. I. Krisko, T. E. Strecker, H-T. Kim, P. H. Brown
Dátum:	2007
ISSN:	0950-9232
Megjegyzések:	The activating protein-1 (AP-1) transcription factor transduces growth signals through signal transduction pathways to the nucleus, leading to the expression of genes involved in growth and malignant transformation in many cell types. We have previously shown that overexpression of a dominant negative form of the cJun proto-oncogene, a cJun dominant negative mutant (Tam67), blocks AP-1 transcriptional activity, induces a G1 cell cycle block and inhibits breast cancer cell growth in vitro and in vivo. We found that AP-1 blockade byTam67 in MCF-7 breast cancer cells downregulates cyclin D1 transcriptional activitybyat least two mechanisms: bysuppressing transcription at the known AP-1 binding site (934/928) and bysuppressing growth factor-induced expression through suppressing E2F activation at the E2F-responsive site (726/719). AP-1 blockade also led to reduced expression of E2F1 and E2F2, but not E2F4, at the mRNA and protein levels. Chromatin immunoprecipitation and supershift assays demonstrated that AP-1 blockade caused decreased binding of E2F1 protein to the E2F site in the cyclin D1 promoter. We also found that Tam67 suppressed the expression of the E2F1 dimerizing partner, DP1 and E2F-upregulated cell cycle genes (cyclins E, A, B and D3) and enhanced the expression of E2F-downregulated cell cycle genes (cyclins G2 and I). Reduced expression of other E2F-regulated genes was also seen with AP-1 blockade and E2F suppression. Thus, the AP-1 factor regulates the expression of cyclin D and E2F (the latter in turn regulates E2F-downstream genes), leading to cell cycle progression and breast cancer cell proliferation.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban AP-1 factor proliferation arrest cyclin D1 E2F factors gene expression regulation breast cancer cells
Megjelenés:	Oncogene. - 27 (2007), p. 366-377. -
További szerzők:	Uray Iván Péter (1970-) (kutatóorvos) Li, Yuxin Krisko, T. I. Strecker, T. E. Kim, HeeTae Brown, Powel H.
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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