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.

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 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.

• Authors: Maria J Chen, Ya-Huei Kuo, X C Tian, Thomas T Chen
• Journal: General and comparative endocrinology (Gen Comp Endocrinol) Vol. 126 Issue 3 Pg. 342-51 (May 2002) ISSN: 0016-6480 [Print] United States
• PMID: 12093122 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2002 Elsevier Science (USA).

Chemical References

• Peptide Fragments
• Protein Precursors
• Recombinant Proteins
• pro-insulin-like growth factor I
• Insulin-Like Growth Factor I

Topics

• Animals
• Cell Division (drug effects)
• Fishes
• Humans
• Insulin-Like Growth Factor I (pharmacology)
• Neoplasm Invasiveness
• Neoplasms (pathology)
• Oncorhynchus mykiss
• Peptide Fragments (pharmacology)
• Polymerase Chain Reaction
• Protein Precursors (pharmacology)
• Recombinant Proteins (pharmacology)
• Transfection
• Tumor Cells, Cultured