YY1 transcription factor is not responsible for the negative regulation of hamster Muc1 transcription.
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.
Hisatsune
Akinori
A
Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, 20 Penn Street, Baltimore, Maryland 21201, USA.
Hyun
Sang Won
SW
Lee
Insong James
IJ
Georas
Steven
S
Kim
K Chul
KC
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
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D018396:Mucin-1; D012333:RNA, Messenger; D014157:Transcription Factors; D050986:YY1 Transcription Factor