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Secretion of an Insulin-like Growth Factor-I-related Protein by Human Breast Cancer Cells

Medical Breast Cancer Section, Medicine Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892 [K. K. H., D. K., M. E. L., R. B. D.]; Baylor College of Medicine, Houston, Texas 77030 [K. H. G.]; and Children's Hospital of San Francisco, San Francisco, California 94119 [E. M. S.]

Somatomedin activity is required for proliferation of normal cells; recently somatomedin activity in the cellular environment was shown to be necessary for expression of the transformed phenotype. We demonstrate here that authentic serum-derived insulin-like growth factor-I (IGF-I) stimulates the proliferation of four human breast cancer cell lines, MCF-7, MDA-MB-231, ZR-75-1, and Hs578T in serum-free monolayer culture and that each of these lines produces and secretes an IGF-I-related growth factor. The two highly tumorigenic estrogen-independent cell lines, MDA-MB-231 and Hs578T, produced 2- to 10-fold more IGF-I than did two estrogen responsive cell lines, MCF-7 and ZR-75-1, which are not tumorigenic in the absence of estrogen. These breast cancer cells also secrete a M_r 50,000 binding activity which partially obscured detection of IGF-I by radioimmunoassay. Acid-ethanol extraction allowed dissociation of the high molecular weight complex; whereupon, fully immunoreactive IGF-I comigrated on acid gel exclusion chromatography with authentic human serum-derived IGF-I. Radioimmunoassay displacement curves for breast cancer cell line-derived IGF-I were parallel to those for authentic IGF-I. Northern blot analysis of mRNA from four breast cancer cell lines demonstrated specific hybridization with a human IGF-I probe corresponding to one of the two major transcripts seen in human liver mRNA. These data suggest that breast cancer cell line-derived IGF-I is similar to liver-synthesized, serumderived IGF-I.

¹ To whom requests for reprints should be addressed, at Medicine Branch, National Cancer Institute, Building 10, Room 12N226, Bethesda, MD 20892.

Received 10/ 4/85. Revised 2/14/86. Revised 5/27/86. Accepted 5/29/86.

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