Basic–alimentary tractReg IV Activates the Epidermal Growth Factor Receptor/Akt/AP-1 Signaling Pathway in Colon Adenocarcinomas
Section snippets
Cell Culture and Proliferation Assay
HCT116 and HT29 colon adenocarcinoma cells (American Type Culture Collection, Manassas, VA) were grown in Dulbecco’s modified Eagle medium (DMEM) containing 10% heat inactivated fetal bovine serum (Sigma Chemical Co, St Louis, MO). Endotoxin-free recombinant human Reg IV (rhR4) was produced in Pichia pastoris by fermentation and purified by tangential flow ultrafiltration and preparative high-performance liquid chromatography as previously described.45 Cells were placed overnight in serum-free
Reg IV Induces Proliferation of HCT116 and HT29 Cells Comparable to That of EGF
Reg IV is overexpressed in colorectal carcinomas16, 17, 18 and regenerating mucosa of patients with Crohn’s disease or ulcerative colitis,10, 47 suggesting a possible role in the regulation of cell proliferation and survival. To determine Reg IV effects on cell growth, we treated HCT116 and HT29 CRC cells with increasing concentrations of rhR4 (0–500 nmol/L) and EGF (0–10 nmol/L) for 72 hours. These cells were initially chosen for the study because they have a responsive EGFR system and are
Discussion
Advanced colorectal adenocarcinoma is generally poorly responsive to chemotherapy and radiation.70, 71 To improve treatment outcomes, a better understanding of the pathways that underlie the behavior of colorectal cancers and contribute to deregulated proliferation and resistance to chemotherapeutic agents and radiation is necessary. Members of the regenerating (Reg) multigene family are potential candidates for regulating these events. Recent studies confirmed the adverse prognostic
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Supported by National Institutes of Health grants DK002457, DK060106, and DK52574 (to B.K.D.) and DK62265 (to S.A., a Research Scholar of the American Gastroenterological Association).