Abstract
To identify molecular alterations implicated in the initiating steps of breast tumorogenesis, we compared the gene expression profiles of normal and ductal carcinoma in situ (DCIS) mammary epithelial cells by using serial analysis of gene expression (SAGE). Through the pair-wise comparison of normal and DCIS SAGE libraries, we identified several differentially expressed genes. Here, we report the characterization of one of these genes, HIN-1 (high in normal-1). HIN-1 expression is significantly down regulated in 94% of human breast carcinomas and in 95% of preinvasive lesions, such as ductal and lobular carcinoma in situ. This decrease in HIN-1 expression is accompanied by hypermethylation of its promoter in the majority of breast cancer cell lines (>90%) and primary tumors (74%). HIN-1 is a putative cytokine with no significant homology to known proteins. Reintroduction of HIN-1 into breast cancer cells inhibits cell growth. These results indicate that HIN-1 is a candidate tumor suppressor gene that is inactivated at high frequency in the earliest stages of breast tumorogenesis.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Northern
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Blotting, Western
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Breast / cytology
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Breast / metabolism*
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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CHO Cells
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COS Cells
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Carcinoma, Ductal, Breast / genetics
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Carcinoma, Ductal, Breast / metabolism*
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Carcinoma, Ductal, Breast / pathology
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Carcinoma, Intraductal, Noninfiltrating / genetics
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Carcinoma, Intraductal, Noninfiltrating / metabolism*
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Carcinoma, Intraductal, Noninfiltrating / pathology
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Carcinoma, Lobular / genetics
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Carcinoma, Lobular / metabolism*
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Carcinoma, Lobular / pathology
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Cell Division
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Cells, Cultured / metabolism
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Chlorocebus aethiops
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Cricetinae
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Cricetulus
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Cytokines / biosynthesis
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Cytokines / genetics
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Cytokines / isolation & purification*
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Cytokines / physiology
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DNA Methylation
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Epithelial Cells / metabolism
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Female
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Gene Expression Profiling*
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Gene Expression Regulation, Neoplastic*
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Gene Library
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Gene Silencing
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Genes, Tumor Suppressor*
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Growth Inhibitors / genetics
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Growth Inhibitors / physiology
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Humans
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Molecular Sequence Data
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / isolation & purification*
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Promoter Regions, Genetic
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RNA, Messenger / biosynthesis
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RNA, Neoplasm / biosynthesis
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Recombinant Fusion Proteins / physiology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Transfection
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Tumor Cells, Cultured / metabolism
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Tumor Suppressor Proteins*
Substances
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Cytokines
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Growth Inhibitors
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Neoplasm Proteins
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RNA, Messenger
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RNA, Neoplasm
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Recombinant Fusion Proteins
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SCGB3A1 protein, human
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Tumor Suppressor Proteins