Ovarian Cancers Express and Process Progastrin

Abstract

Gastrin synthesis in ovarian tumors has been described in a few isolated cases associated with the Zollinger-Ellison syndrome. Consequently, ovarian gastrin synthesis has been considered exceptional. In order to evaluate whether expression of gastrin in ovarian tumors indeed is rare, we examined the expression and processing of progastrin in 16 malignant and 5 benign ovarian tumors and 4 normal postmenopausal ovaria. Using a library of sequence specific radioimmunoassays, cleavage by processing-like enzymes, and gel chromatography, we found that one-half of the malignant tumors expressed significant concentrations of amidated gastrins [6.7 ± 2.7 (SEM) pmol/g; range, 1.4–20.0 pmol/g, n = 7]. The concentrations of glycine-extended gastrins and progastrins were low (0.25 ± 0.03 and 1.4 ± 0.4 pmol/g, respectively) but higher than in controls and benign tumors. Chromatography showed that the majority of the bioactive gastrins was unsulfated gastrin-17. The other half of the malignant tumors expressed glycine-extended gastrins and progastrins (0.2 ± 0.03 and 0.6 ± 0.1 pmol/g; n = 9), but the amidation of the peptides was impaired (0.1 ± 0.03 pmol/g). Low concentrations of glycine-extended gastrins and progastrins were detected in the normal ovarian tissues (0.2 ± 0.05 pmol/g tissue and 0.2 ± 0.06 pmol/g, respectively, n = 4) and in the benign tumors (0.1 ± 0.02 pmol/g and 0.5 ± 0.03 pmol/g; n = 5). Amidated gastrins were undetectable, except in low amounts in a single benign tumor (0.2 pmol/g tissue). The results show that postmenopausal ovaria and neoplastic ovarian tissues express the gastrin gene at peptide level. The synthesis and processing of progastrin increase considerably in malignant tumors.