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Widespread Loss of Gelsolin in Breast Cancers of Humans, Mice, and Rats¹

Departments of Experimental Pathology [H. L. A., K. L. H., Y. D., F. N., B. B. A.] and Pathology [J. S. W.], Roswell Park Cancer Institute, Buffalo, New York 14263, and Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215 [J. L. C.]

Down-regulation of gelsolin, an actin-binding protein, is frequently found in several types of transformed cells and tumors. The present study demonstrates that gelsolin protein and RNA were absent or markedly reduced in human breast cancer cell lines relative to "normal" mortal human mammary epithelial cells and benign, immortalized cell lines. Moreover, actin filaments were usually attenuated coincident with the reduction in gelsolin. Gelsolin was also missing or greatly decreased in 70% of 30 human sporadic, invasive breast carcinomas examined by immunocytochemistry and in 100% of virally induced mouse and chemically induced rat mammary carcinomas evaluated by Northern analysis. Southern analysis revealed no major mutations in the gelsolin gene of human breast cancer cells. Our results show that partial or total loss of gelsolin expression is common to the majority of breast cancers of diverse etiologies in three animal species and point to gelsolin as a candidate suppressor of breast cancer.

¹ Supported by the Roswell Park Alliance Foundation and Grants CA56609 and CA62014 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed.

Received 8/ 8/96. Accepted 9/18/96.

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