The zinc-finger transcription factor Snail downregulates proliferating cell nuclear antigen expression in colorectal carcinoma cells.
The Snail family of zinc-finger protein is a transcription repressor that is involved in the development of vertebrate and invertebrate embryos as well as in tumor progression. This family leads to broad biological functions such as cell differentiation, cell motility, cell cycle regulation and apoptosis. However, the target genes of Snail remain little known. In this study, we found several potential Snail binding sequences in the 5'-flanking region of human PCNA gene. Cotransfection experiments showed that Snail reduces human PCNA gene promoter activity in colorectal carcinoma cell lines, HCT116 and Colo320HSR. Snail-reduced PCNA expression was detected in immunoblotting and immunochemistry. In BrdU incorporation experiment, Snail inhibited the BrdU incorporation. Electrophoretic mobility shift assays showed that Snail can bind to the potential Snail recognition sites in the human PCNA promoter. Taken together, our results suggest that Snail may have an inhibitory effect on cell proliferation through down-regulation of PCNA expression as a novel target.
Park
Jae-Hong
JH
Department of Molecular Biology, Pusan National University, Busan 609-735, Korea.
Sung
Ik-Joo
IJ
Lee
Sae-Won
SW
Kim
Kyu-Won
KW
Kim
Young-Shin
YS
Yoo
Mi-Ae
MA
D024506:5' Flanking Region; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*
D018809:Proliferating Cell Nuclear Antigen; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors