Novel Expression and Regulation of Gastrin Gene in Human Ovarian Cancer Cell Line, SW626

Abstract

Gastrin-secreting tumors have been identified inectopic locations including the ovary; the mechanismsregulating gastrin gene expression, its distribution,and signaling pathways in these ectopic tissues are not known. The purpose of our present studywas to determine: (1) whether the gastrin gene andpeptide could be detected in ovarian cancer cell lines,(2) if functional gastrin releasing peptide receptors (GRP-R) are present, and (3) whether gastringene expression is altered by GRP. Five ovarian cancercell lines (SW626, OVCA 420, OVCA 429, OVCA 432, andOVCA 433) were analyzed. We identified gastrin gene and peptide expression in the SW626 cell linebut not in the OVCA lines. SW626 cells express afunctional GRP-R that is correctly coupled to theCa²⁺ signaling pathway. Treatment of SW626cells with bombesin, the amphibian equivalent of GRP, inhibitedexpression of the gastrin gene in a time- anddose-dependent fashion. The SW626 ovarian cancer cellline will provide a useful model to further defineregulation and expression of both the gastrin gene andpeptide in ectopic (nongastrointestinal)tissues.