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HL-60-derived apoptosis inducing factor
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[EGFR-related protein; EGF receptor-related protein] The cDNA encoding ERRP has been isolated from the rat gastroduodenal mucosa (Yu et al, 2001). The encoded protein (479 amino acids) shows approximately 85 % homology to the external domain of the rat EGF receptor.
ERRP is present in most, if not all, normal human epithelial cells. Overexpression of ERRP in the colon cancer cell line, HCT116, markedly reduces proliferation in monolayers and colony formation in soft agar (see also: colony formation assay). In another colon cancer cell line, Caco-2, expression of ERRP is associated with a marked reduction in EGF receptor activation and cell proliferation. ERRP may play a role in regulating cell proliferation by modulating the function of EGF receptors.
Xu et al (2005) have reported that ERRP is an effective inhibitor of various erbB receptors, which blocks proliferation of colon and breast cancer cells expressing EGF receptors, HER2, or HER4). Thus, ERRP may be a potential therapeutic agent for a wide variety of epithelial cancers expressing different levels and subclasses of EGF receptors. Also, ERPP causes significant cell death by apoptosis in these cells.
Zhang et al (2005) have reported that ERRP inhibits cell growth and induces apoptosis of BxPC3 pancreatic cancer cells. Low levels of ERRP are associated with poor clinical outcome in patients with aggressively growing pancreatic carcinoma (Feng et al, 2002). Marciniak et al (2004) have reported that ERRP inhibits the growth of prostate cancer cells by attenuating EGF receptor signaling processes. Expression of ERRP in gastric cancer cells and hepatocellular carcinomas is reduced and inversely correlates with cell proliferation and grade of malignancy (Moon et al, 2004, 2005).
Schmelz et al (2004) have reported that loss of ERRP expression is a common event during aging and early stages of chemically induced colon cancer. Thus, loss of ERRP be be a risk factor also for developing colorectal cancer in the older population. Levi et al (2004) have reported that ERRP causes cell cycle arrest and induces apoptosis of human colon cancer cells xenotransplanted into nude mice. Marciniak et al (2003) have reported that intratumoral or subcutaneous injections of purified ERRP causes regression of palpable colon cancer xenograft tumors in some severely compromised immunodeficient mice and arrests tumor growth in others.
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ENTRY LAST MODIFIED: June 2005
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