DIFFERENTIAL EXPRESSION OF ELAFIN IN HUMAN NORMAL MAMMARY EPITHELIAL-CELLS AND CARCINOMAS IS REGULATED AT THE TRANSCRIPTIONAL LEVEL

Elafin is an elastase inhibitor with a unique structure, not related t o the serpin family, which includes the neutrophil elastase inhibitor. The gene was identified in this laboratory by subtractive hybridizati on between RNAs from human mammary tumor-derived cells and cDNAs from normal human mammary epithelial cells. Elafin is consistently expresse d in normal mammary epithelial cells, but is down-regulated in most br east tumor cell lines. Restriction fragment analysis detected no gross deletions or rearrangement of the gene in any of the tumor cell lines examined. The elafin gene was cloned, and both the cDNA and the promo ter region were sequenced. A major positive upstream promoter element was identified by chloramphenicol acetyltransferase assay and deletion analysis, active in normal cell extracts but not in extracts of tumor cells. These results demonstrate that differential expression of elaf in in normal mammary epithelial cells and breast tumor cells is regula ted at the transcriptional level. Cell synchronization experiments dem onstrated that elafin mRNA is down-regulated in S phase in normal cell s. These results suggest that elafin may act as an inhibitor of cell c ycle progression.