p53 activates expression of HIC-1, a new candidate tumour suppressor gene on 17p13.3.
For several human tumour types, allelic loss data suggest that one or more tumour suppressor genes reside telomeric to the p53 gene at chromosome 17p13.1. In the present study we have used a new strategy, involving molecular analysis of a DNA site hypermethylated in tumour DNA, to identify a candidate gene in this region (17p13.3). Our approach has led to identification of HIC-1 (hypermethylated in cancer), a new zinc-finger transcription factor gene which is ubiquitously expressed in normal tissues, but underexpressed in different tumour cells where it is hypermethylated. Multiple characteristics of this gene, including the presence of a p53 binding site in the 5' flanking region, activation of the gene by expression of a wild-type p53 gene and suppression of G418 selectability of cultured brain, breast and colon cancer cells following insertion of the gene, make HIC-1 gene a strong candidate for a tumour suppressor gene in region 17p13.3.
Wales
M M
MM
Human Genetics Graduate Program, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
Biel
M A
MA
el Deiry
W
W
Nelkin
B D
BD
Issa
J P
JP
Cavenee
W K
WK
Kuerbitz
S J
SJ
Baylin
S B
SB
D000595:Amino Acid Sequence; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002886:Chromosomes, Human, Pair 17; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008745:Methylation; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics*
D006131:Growth Inhibitors; C096870:Hic1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D011994:Recombinant Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53