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 bre ast tumorogenesis, we compared the gene expression profiles of normal and d uctal carcinoma in situ (DCIS) mammary epithelial cells by using serial ana lysis of gene expression (SAGE). Through the pair-wise comparison of normal and DCIS SAGE libraries, we identified several differentially expressed ge nes. Here, we report the characterization of one of these genes, HIN-1 (hig h 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 a nd lobular carcinoma in situ. This decrease in HIN-1 expression is accompan ied by hypermethylation of its promoter in the majority of breast cancer ce ll lines (> 90%) and primary tumors (74%). HIN-1 is a putative cytokine wit h no significant homology to known proteins. Reintroduction of HIN-1 into b reast 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.