Biological activity of rainbow trout Ea4-peptide of the pro-insulin-like growth factor (pro-IGF)-I on promoting attachment of breast cancer cells (MDA-MB-231) via alpha2- and beta1-integrin.

Abstract

E-peptide of pro-IGF-I was considered as biologically inactive. We have demonstrated that rainbow trout (rt) Ea4-peptide exerted biological activities in several established tumor cell lines [Chen et al., 2002; Kuo and Chen, 2002]. Here we report the activity of rtEa4-peptide in promoting attachment of human breast cancer cells (MDA-MB-231). While rtEa2-, rtEa3-, and rtEa4-peptides enhanced the attachment of MDA-MB-231 cells in a dose dependent manner, rtEa4-peptide possessed the highest activity. Antibodies specific to alpha2 and beta1 integrins significantly inhibited the attachment of cells to rtEa4-peptide coated-plates by 40%. In addition, rtEa4-peptide induced the expression of fibronectin 1 and laminin receptor genes in MDA-MB-231 cells. Blocking new protein synthesis by cycloheximide significantly reduced the attachment of MDA-MB-231 cells to rtEa4-peptide coated wells by 50%. These results suggest that rtEa4-peptide may promote cell attachment by interacting with alpha2/beta1 integrin receptors at the cell surface and by inducing the expression of fibronectin 1 and laminin receptor genes. Expression of fibronectin 1 gene induced by rtEa4-peptide in MDA-MB-231 cells was abolished by inhibitors of PI3K, PKC, Mek1/2, JNK1/2, and p38 MAPK signaling transduction molecules. These results suggested that induction of fibronectin 1 gene expression in MDA-MB-231 cells by rtEa4-peptide may be mediated via PI3K, PKC, Mek1/2, JNK1/2, and p38 MAPK signal transduction molecules.

• Authors: Sineenat Siri, Maria J Chen, Thomas T Chen
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 99 Issue 6 Pg. 1524-35 (Dec 15 2006) ISSN: 0730-2312 [Print] United States
• PMID: 16817231 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: (c) 2006 Wiley-Liss, Inc.

Chemical References

• DNA Primers
• Integrin alpha2
• Integrin alpha5beta1
• Integrin beta1
• Receptors, Laminin
• Recombinant Proteins
• Insulin-Like Growth Factor I

Topics

• Animals
• Base Sequence
• Breast Neoplasms (pathology)
• Cell Line, Tumor
• DNA Primers
• Gene Expression Regulation (drug effects)
• Humans
• Insulin-Like Growth Factor I (pharmacology)
• Integrin alpha2 (physiology)
• Integrin alpha5beta1 (genetics)
• Integrin beta1 (physiology)
• Oncorhynchus mykiss
• Receptors, Laminin (genetics)
• Recombinant Proteins (isolation & purification, pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction