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

Abstract

Fusion of tumorigenic HeLa cells with human skin fibroblasts results in chromosomally stable hybrids that are nontumorigenic and no longer express the HeLa tumor-associated marker intestinal alkaline phosphatase (IAP). Previous studies of spontaneous tumorigenic segregants from the nontumorigenic hybrids implicated the loss of one copy of human fibroblast chromosome 11 in the concomitant reexpression of tumorigenicity. In an attempt to identify genes involved in the control of tumorigenic expression, we performed differential display screening of nontumorigenic hybrid cells and tumorigenic segregants. Subsequent northern blot analyses reproducibly showed 17 differentially expressed genes, eight of which were expressed differentially in the nontumorigenic hybrids and nine of which were expressed differentially in the tumorigenic hybrids. The former were genes for 80K-L protein (a substrate of protein kinase C), AXL/UFO (a receptor tyrosine kinase), insulin-like growth factor binding protein 3, apolipoprotein AI regulatory protein, collagen type I alpha-2 chain, transforming growth factor-beta-induced gene product 3 (BIGH3), pregnancy-specific beta-1-glycoprotein, and fibroblast activation protein alpha. The latter nine genes were genes for serum/glucocorticoid-regulated kinase (SGK; a serine/threonine protein kinase), PTPCAAX1 (a tyrosine phosphatase), CXCR-4 (a G-protein-coupled membrane receptor), L-kynurenine hydrolase, beta-1, 4-galactosyltransferase, keratin 8, keratin 17, and H19 and a novel gene. The differential expression of these genes provided several interesting candidates for regulation of tumorigenic expression, including those involved in signal transduction and the extracellular matrix, cytoskeletal proteins, cell-surface enzyme, and the H19 gene.

FAPα, a surface peptidase expressed during wound healing, is a tumor suppressor

“…A second independent observation from studies of somatic cell hybrids between normal fibroblasts and HeLa carcinoma cells identified Fap as a potential inhibitor of tumorigenesis (Tsujimoto et al, 1999). Fap was one of eight genes differentially expressed in nontumorigenic hybrid lines, consistent with the hypothesis that Fap is involved in suppressing the tumorigenic phenotype.…”

Identify lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines using gene chip

“…These indicated that Axl might be related to the tumorigenesis and tumor progression. Sgk, a serine/threonine protein kinase, was found up-regulation in the tumorigenic HeLa cells compared to nontumorigenic HeLa cells which came from fusion of tumorigenic HeLa cells with human skin fibroblasts [55] . Male germ cellassociated kinase (Mak) was shown to be up-regulated in prostate cancer cell lines than those of normal prostate epithelial cells [56] .…”

Overexpression of fibroblast activation protein and its clinical implications in patients with osteosarcoma

“…Ramirez‐Montagut et al observed that FAP expression or a catalytic mutant of FAP might decrease the tumorigenicity of mouse melanoma cells in animals and restored contact inhibition and growth factor dependence. Tsujimoto et al identified FAP as a potential inhibitor of tumorigenesis of HeLa carcinoma cells. Taken together, there is an obvious discrepancy between FAP function in tumor promotion and tumor suppression.…”