HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells.
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.
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- Tumor Suppressor Proteins
- Tumor Cells, Cultured
- Transfection
- Sequence Homology, Amino Acid
- Sequence Alignment
- Recombinant Fusion Proteins
- RNA, Neoplasm
- RNA, Messenger
- Promoter Regions, Genetic
- Neoplasm Proteins
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Suppressor Proteins
- Tumor Cells, Cultured
- Transfection
- Sequence Homology, Amino Acid
- Sequence Alignment
- Recombinant Fusion Proteins
- RNA, Neoplasm
- RNA, Messenger
- Promoter Regions, Genetic
- Neoplasm Proteins