Inhibition of human breast cancer cell (MBA-MD-231) invasion by the Ea4-peptide of rainbow trout pro-IGF-I.
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.
Siri
Sineenat
S
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269, USA.
Chen
Maria J
MJ
Chen
Thomas T
TT
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D017686:Oncorhynchus mykiss; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D011498:Protein Precursors; C119953:pro-insulin-like growth factor I; D007334:Insulin-Like Growth Factor I; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator