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Differential Expression of Elafin in Human Normal Mammary Epithelial Cells and Carcinomas Is Regulated at the Transcriptional Level¹

Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115

Elafin is an elastase inhibitor with a unique structure, not related to the serpin family, which includes the neutrophil elastase inhibitor. The gene was identified in this laboratory by subtractive hybridization between RNAs from human mammary tumor-derived cells and cDNAs from normal human mammary epithelial cells. Elafin is consistently expressed in normal mammary epithelial cells, but is down-regulated in most breast 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 promoter 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 elafin in normal mammary epithelial cells and breast tumor cells is regulated at the transcriptional level. Cell synchronization experiments demonstrated that elafin mRNA is down-regulated in S phase in normal cells. These results suggest that elafin may act as an inhibitor of cell cycle progression.

¹ This work was supported in part by NIH Grant CA9513901 (R. S.) and a NRSA Fellowship 5-T32-CA09361-14 (M. Z.).

² Present address: Surgery Branch, National Cancer Institute, Bethesda, MD 20892.

³ To whom requests for reprints should be addressed, at Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.

Received 4/19/95. Accepted 5/ 5/95.

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