The Effects of Gastrin and Hox-A1 on HT-29 Cell Proliferation

Abstract

Gastrin is a gastrointestinal peptide hormone synthesized in G cells and secreted in the antrum of the stomach. Though its primary role is to stimulate the secretion of gastric acid by parietal cells, it is also involved in the maintenance of cellular identity and proliferation of gastrointestinal tissue in the stomach, pancreas, and duodenum. Aberrant expression of gastrin has been associated with increased rates of cancer, and more specifically colon cancer. While some of the effects are due to the mature amidated form of the peptide, G17-NH2, its incompletely processed precursors have been shown to have oncogenic functions as well. In this investigation, we focus on glycine-extended gastrin 17 (G17-Gly), one of the most characterized precursors, and how its role in cellular proliferation compares to G17-NH2. Both forms can induce cell proliferation; however, the mechanisms by which these peptides act are not well defined. In this study, we explored the relationship of both gastrin forms with respect to Hox-A1, a homeodomain containing transcription factor known to be important in cell growth and differentiation. G17-NH2 (+44%) and G17-Gly (+35%) significantly increased cell proliferation in the human colon adenocarcinoma cell line, HT-29. Quantitative real time polymerase chain reaction (qRT-PCR) and western blot analysis indicated that these effects were not associated with altered Hox-A1 expression. Lastly, RNA interference suggested that HT-29 and gastrin-stimulated growth were not dependent on Hox-A1.