title: YY1 transcription factor is not responsible for the negative regulation of hamster Muc1 transcription.
abstract: Muc1 is the cell surface glycoprotein abundantly expressed in cancer cells and has been shown to be involved in tumor metastasis and promotion. Recently, we identified a 37 bp segment on the hamster Muc1 promoter with the ability to suppress Muc1 transcription. This 37 bp putative negative regulatory element (NRE) binds to a transcriptional regulator Yin Yang 1 (YY1). In the present study, we examined whether binding of YY1 is responsible for the negative regulatory effect by the 37 bp segment using a hamster pancreatic cancer cell line, HP-1 cells, transfected with various expression plasmid constructs. Our results showed that: (1) overexpression of YY1 up-regulated the transcriptional activity of the full-length hamster Muc1 promoter in a dose-dependent manner; (2) the mutation of the YY1 binding site did not affect either the basal transcriptional activity or the increased transcriptional activity by YY1; and (3) even the deletion of the 37 bp NRE segment could not abrogate the increased transcriptional activity by YY1. We conclude that the NRE acts in a YY1-independent manner and that YY1 instead enhances Muc1 transcriptional activity. Further study of the precise mechanism by which YY1 augments Muc1 gene expression should be worthwhile.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, Maryland 21201, USA.
authors.forename: Akinori
authors.initials: A
authors.lastname: Hisatsune
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Hyun
authors.forename: Insong James
authors.initials: IJ
authors.lastname: Lee
authors.forename: Steven
authors.initials: S
authors.lastname: Georas
authors.forename: K Chul
authors.initials: KC
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D018396:Mucin-1 / Q000235:genetics*; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D050986:YY1 Transcription Factor
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D018396:Mucin-1; D012333:RNA, Messenger; D014157:Transcription Factors; D050986:YY1 Transcription Factor