PMID: 11912171Mar 26, 2002Paper

Fibroblast growth factor receptor 1 phosphotyrosine 766: molecular target for prevention of progression of prostate tumors to malignancy

Cancer Research
Fen WangWallace L McKeehan

Abstract

Dissection of processes that promote the slow progression to malignancy from those that drive the malignant phenotype, once acquired, is important for identification of molecular targets for rational design of dietary and pharmaceutical intervention to hold premalignant cancer in check. In adult parenchymal organs, fibroblast growth factor receptor (FGFR) kinase isotypes are partitioned between stroma and epithelium, respectively, and mediate communication between the two compartments to maintain organ homeostasis. The ectopic appearance of stromal FGFR1 is a hallmark of epithelial cells from model transplantable rat prostate tumors that progress to malignancy. Here we show that, despite the fact that it is transcriptionally active, the appearance of FGFR1 in nonmalignant prostate tumor epithelial cells at first does not drive cell proliferation or support a malignant phenotype. These properties develop over time with proliferative aging of the cell population coincident with FGFR1-dependent activation of the mitogen-activated protein kinase signaling pathway. Phospholipase Cgamma-interactive phosphotyrosine 766 of FGFR1 is required for the age-dependent acquisition of the proliferative response to FGFR1, although it appears no...Continue Reading

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