Differential gene expression in tumorigenic and nontumorigenic HeLa x normal human fibroblast hybrid cells

Fusion of tumorigenic HeLa cells with human skin fibroblasts results in chr omosomally stable hybrids that are nontumorigenic and no longer express the HeLa tumor-associated marker intestinal alkaline phosphatase (IAP). Previo us studies of spontaneous tumorigenic segregants from the nontumorigenic hy brids implicated the loss of one copy of human fibroblast chromosome 11 in the concomitant reexpression of tumorigenicity. In an attempt to identify g enes involved in the control of tumorigenic expression, we performed differ ential display screening of nontumorigenic hybrid cells and tumorigenic seg regants. Subsequent northern blot analyses reproducibly showed 17 different ially expressed genes, eight of which were expressed differentially in the nontumorigenic hybrids and nine of which were expressed differentially in t he tumorigenic hybrids. The former were genes for 80K-L protein (a substrat e of protein kinase C), AXL/UFO (a receptor tyrosine kinase), insulin-like growth factor binding protein 3, apolipoprotein Al regulatory protein, coll agen type I alpha-2 chain, transforming growth factor-beta-induced gene pro duct 3 (BIGH3), pregnancy-specific beta-1-glycoprotein, and fibroblast acti vation protein alpha. The latter nine genes were genes for serum/glucocorti coid-regulated kinase (SGK; a serine/threonine protein kinase), PTPCAAX1 (a tyrosine phosphatase), CXCR-4 (a G-protein-coupled membrane receptor), L-k ynurenine hydrolase, beta-1,4-galactosyltransferase, keratin 8, keratin 17, and H19 and a novel gene. The differential expression of these genes provi ded several interesting candidates for regulation of tumorigenic expression , including those involved in signal transduction and the extracellular mat rix, cytoskeletal proteins, cell-surface enzyme, and the H19 gene. Mol. Car cinog. 26:298-304, 1999. (C) 1999 Wiley-Liss, Inc.