This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van Solinge, W. W. Articles by Rehfeld, J. F. Search for Related Content PubMed PubMed Citation Articles by van Solinge, W. W. Articles by Rehfeld, J. F.

Ovarian Cancers Express and Process Progastrin¹

University Department of Clinical Biochemistry, Rigshospitalet, DK-2100 Copenhagen, Denmark

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.

¹ The study was supported by grants from the Danish Medical Research Council; the Danish Cancer Union; and the Alfred Benzon, Carlsberg, Gangsted, NOVO, and Vissing Foundations.

² To whom requests for reprints should be addressed, at Department of Clinical Biochemistry (KK-3011), Rigshospitalet, DK-2100 Copenhagen, Denmark.

Received 9/24/92. Accepted 2/ 1/93.

This article has been cited by other articles:

				W. Rengifo-Cam, S. Umar, S. Sarkar, and P. Singh Antiapoptotic Effects of Progastrin on Pancreatic Cancer Cells Are Mediated by Sustained Activation of Nuclear Factor-{kappa}B Cancer Res., August 1, 2007; 67(15): 7266 - 7274. [Abstract] [Full Text] [PDF]

				V. M. Stepan, D. F. Krametter, M. Matsushima, A. Todisco, J. Delvalle, and C. J. Dickinson Glycine-extended gastrin regulates HEK cell growth Am J Physiol Regulatory Integrative Comp Physiol, August 1, 1999; 277(2): R572 - R581. [Abstract] [Full Text] [PDF]

				J. F. REHFELD The New Biology of Gastrointestinal Hormones Physiol Rev, October 1, 1998; 78(4): 1087 - 1108. [Abstract] [Full Text] [PDF]