Heparin-Binding (Fibroblast) Growth Factor/Receptor Gene Expression in the Prostate
Heparin-binding (fibroblast) growth factors (HBGF) play both autocrine and paracrine roles in growth of normal and tumor prostate epithelial and mesenchymal cells. In the rat, expression of HBGF-1 dominates in normal tissue and slow-growing Dunning prostate tumor tissues. Both HBGF-1 and HBGF-2 are expressed in fast-growing, malignant variants of the Dunning tumor. Expression of HBGF-1 occurs in young normal prostate epithelial cells and disappears with age. Slow-growing Dunning tumor mesenchymal cells, not epithelial cells, constitutively express HBGF-1. HBGF requirement and receptor phenotype is altered in tumor epithelial cells. In contrast to IGF-1 and the Elg/Bek/Cek gene product, a candidate HBGF receptor, neither HBGF-1 nor HBGF-2 expression in normal and tumor tissues increases during androgenstimulated growth. Flg/Bek/Cek is expressed in young prostates, during androgen-stimulated growth of adult prostate, constitutively in tumors, and appears limited to the stromal cell fraction of the slow-growing tumors. Expression is elevated in the fast-growing, highly malignant tumors. Normal and slow-growing tumor epithelial cells have receptor sites for HBGF that may differ from Flg/Bek/Cek. Similar to rat prostate tissue, HBGF-1 expression dominates in young human prostate tissue. However, both HBGF-1 and HBGF-2 mRNA as well as the Flg/Bek/Cek gene are detectable in adult human prostate tissue. These differences in rat and human tissue may reflect differences in the epithelial:stromal cell ratio in prostates of the two species.
KeywordsMesenchymal Cell Cholera Toxin Prostate Tissue Normal Prostate Tumor Epithelial Cell
Unable to display preview. Download preview PDF.
- 1.McKeehan, W.L., Adams, P.S., and Rosser, M.P. Modified nutrient medium MCDB 151, dermed growth factors, cholera toxin, pituitary factors, and horse serum support epithelial cell and suppress fibroblast proliferation in primary cultures of rat ventral prostate cells. In Vitro 18:87–91, 1982.PubMedCrossRefGoogle Scholar
- 2.McKeehan, W.L., Adams, P.S., and Rosser, M.P. Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid, cholera toxin, unknown pituitary factors and possibly prolactin, but not androgen, on normal prostate epithelial cells in serum-free, primary cell culture. Cancer Res. 44:1998–2010, 1984.PubMedGoogle Scholar
- 11.Kan, M., DiSorbo, D., Hou, J., Hoshi, H., Mansson, P.E. and McKeehan, W.L. High-and lowaffinity binding of heparin-binding growth factor to a 130 kD receptor correlates with stimulation and inhibition of growth of a differentiated human hepatoma cell. J. Biol. Chem. 263:11306–11313, 1988.PubMedGoogle Scholar
- 13.Ruta, M., Howk, R., Ricca, G., Drohan, W., Zabelshansky, M., Laureys, G., Barton, D.E., Francke, U., Schlessinger, J., and Givol, D. A novel protein tyrosine kinase whose expression is modulated during endothelial cell differentiation. Oncogene 3:9–15, 1988.Google Scholar
- 20.Kan, M., Huang, J., Mansson, P.E., Yasumitsu, H., Carr, B., and McKeehan, W.L. Heparinbinding growth factor type 1 (acidic fibroblast growth factor): A potential biphasic autocrine and paracrine regulator of hepatocyte regeneration. Proc. Natl. Acad. Sci. USA 86:7432–7436, 1989.PubMedCrossRefGoogle Scholar