IngentaConnect Novel biological activities of the fish pro-IGF-I E-peptides: stu...

Abstract:

E-peptides of proinsulin-like growth factor-I (pro-IGF-I) are proteolytically cleaved from the prohormone after translation and have long been regarded as biologically inactive. Tian et al. [Endocrinology 140 (1999) 3387–3390] recently demonstrated that recombinant rainbow trout pro-IGF-I E-peptides (rtEa-2-, rtEa-3-, and rtEa-4-peptides), like hIGF-I, exhibited a dose-dependent mitogenic activity in several nontransformed mammalian cell lines. We show in this report that treatment of established human and fish cancer cells (MCF-7, HT-29, HepG2, ZR-75-1, SK-N-F1, and HC) and retroviral transformed human embryonic kidney cells (293GP) with recombinant rtEa-2- or rtEa-4-, but not rtEa-3-peptide, resulted in a dose-dependent induction of morphological change and enhanced cell attachment. The E-peptide-induced morphological changes are sensitive to treatment with -amanitin or cycloheximide, known inhibitors of RNA and protein synthesis. The in vitro colony formation activity of established human tumor cells (HT-29 and MDA-MB-231) is greatly reduced or diminished by treatment with the rtEa-4-peptide. Both morphological change and reduction of colony formation activity in MDA-MB-231 cells were also observed following transfection with an Ea-4 transgene construct. Furthermore, the invasive activity of HT1080 cells, known invasive cancer cells, is reduced three to fourfold by treatment with the rtEa-4-peptide. These results suggest that E-peptides of rainbow trout pro-IGF-I possess novel biological activities controlling malignant properties of cancer cells in vitro.

Language: English

Document Type: Research article

Affiliations: 1: Department of Molecular and Cell Biology, Biotechnology Center, University of Connecticut, 184 Auditorium Road, U-149 Storrs, CT 06269-3149, USA 2: Department of Animal Science, University of Connecticut, Storrs, CT 06269-3149, USA

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Novel biological activities of the fish pro-IGF-I E-peptides: studies on effects of fish pro-IGF-I E-peptide on morphological change, anchorage-dependent cell division, and invasiveness in tumor cells