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.
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 alpha-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.
Chen
Maria J
MJ
Department of Molecular and Cell Biology, Biotechnology Center, University of Connecticut, 184 Auditorium Road, U-149 Storrs, CT 06269-3149, USA.
Kuo
Ya-Huei
YH
Tian
X C
XC
Chen
Thomas T
TT
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D005399:Fishes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000473:pathology*; D017686:Oncorhynchus mykiss; D010446:Peptide Fragments / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; C119953:pro-insulin-like growth factor I; D007334:Insulin-Like Growth Factor I