Inhibition of human breast cancer cell (MBA-MD-231) invasion by the Ea4-peptide of rainbow trout pro-IGF-I.

Abstract

It was shown previously that Ea4-peptide of trout pro-IGF-I exerted mitogenic activity in non-transformed cells and inhibited colony formation in a soft agar medium of established human cancer cells. Here we report that the same peptide inhibits the invasion of human breast cancer cells (MDA-MB-231) through a matrigel membrane in a dose-dependent manner. The expression of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI1) genes in MDA-MB-231 cells were downregulated by treatment with rtEa4-peptide. The inhibition of expression of these genes in response to rtEa4-peptide treatment was reduced to the control level when inhibitors for c-Jun N-terminal kinase 1/2 (JNK1/2), mitogen activated protein kinase kinase 1/2 (Mek1/2), p38 mitogen activated protein kinase (p38 MAPK), phosphatidylinositol 3-kinase (PI3K), and phosphokinase C (PKC) were used. These results suggest that inhibition of invasion of MDA-MB-231 cells by rtEa4-peptide may be mediated via the suppression of uPA, tPA, and PAI1 gene activities through signal transduction pathways.

• Authors: Sineenat Siri, Maria J Chen, Thomas T Chen
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 99 Issue 5 Pg. 1363-73 (Dec 01 2006) ISSN: 0730-2312 [Print] United States
• PMID: 16795042 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: 2006 Wiley-Liss, Inc.

Chemical References

• Enzyme Inhibitors
• Peptides
• Plasminogen Activator Inhibitor 1
• Protein Precursors
• pro-insulin-like growth factor I
• Insulin-Like Growth Factor I
• Tissue Plasminogen Activator
• Urokinase-Type Plasminogen Activator

Topics

• Animals
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor (drug effects)
• Enzyme Inhibitors (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Insulin-Like Growth Factor I (genetics, metabolism, pharmacology)
• Neoplasm Invasiveness
• Oncorhynchus mykiss
• Peptides (genetics, metabolism, pharmacology)
• Plasminogen Activator Inhibitor 1 (genetics, metabolism)
• Protein Precursors (genetics, metabolism, pharmacology)
• Signal Transduction (physiology)
• Tissue Plasminogen Activator (genetics, metabolism)
• Urokinase-Type Plasminogen Activator (genetics, metabolism)