Activation of growth factor secretion in tumorigenic states of breast cancer induced by 17β-estradiol or v-Ha-ras oncogene

R. B. Dickson, A. Kasid, K. K. Huff, S. E. Bates, C. Knabbe, D. Bronzert, E. P. Gelmann, M. E. Lippman

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Abstract

The MCF-7 human breast cancer cell line responds to estrogen stimulation in vitro by increased secretion of growth factors and proliferation and in vivo by tumor formation in the nude mouse. To test a possible role of growth factor secretion in expression of the tumorigenic phenotype, we stably transfected MCF-7 cells with the v-Ha-ras oncogene to produce the MCF-7ras cell line. The MCF-7ras cell line was tumorigenic in the absence of estrogens and secreted 3- to 5-fold elevated levels of a high molecular weight form of a type α transforming growth factor-like growth factor, type β transforming growth factor, and insulin-like growth factor I. MCF-7ras cells, in contrast to MCF-7, were less sensitive to further growth stimulation by estrogen, type α transforming growth factor, and insulin-like growth factor I and showed little change in receptor levels for these hormones. Conditioned medium from MCF-7ras cells as well as two of its component growth factors (insulin-like growth factor I and type α transforming growth factor) replaced estrogen in stimulating MCF-7 colony formation in vitro. A coordinate increase in growth factor secretion by human breast cancer may contribute to its escape from estrogen dependence.

Original languageEnglish (US)
Pages (from-to)837-841
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume84
Issue number3
DOIs
StatePublished - May 12 1987

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