Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression. Breast Cancer Res Treat 2004 Jan;83(2):161-70
Date
03/05/2004Pubmed ID
14997047DOI
10.1023/b:brea.0000010709.31256.c6Scopus ID
2-s2.0-0742304062 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
In MCF-7L cells, insulin-like growth factor-I (IGF-I) stimulates activation of insulin receptor substrate-1 (IRS-1) and enhances cell proliferation. While others have shown that IGF-I enhances cell motility in MCF-7 cells, we have not been able to demonstrate this. To determine if the source of MCF-7 cells account for these reported differences, we examined the MCF-7 cells available from the American Type Culture Collection (MCF-7/ATCC) and compared them to the MCF-7L cells maintained in our laboratory. Both MCF-7L and MCF-7/ATCC grew in response to 5 nM IGF-I and 1 nM estradiol. However, only MCF-7/ATCC demonstrated IGF-I stimulated motility. Immunoprecipitation of IRS substrates followed by anti-phosphotyrosine blotting demonstrated that both IRS-1 and IRS-2 were activated by IGF-I in these cells. However, MCF-7/ATCC cells had greater phosphorylation of IRS-2 compared to MCF-7L. Immunoblots showed that levels of IRS-1 and IRS-2 were comparable between cell lines. We have previously shown that fibronectin-binding integrins are necessary for IGF-stimulated motility. Similar levels of beta1 integrin were detected in both strains of MCF-7. However, low levels of alpha5 and alpha3 were detected in MCF-7L cells whereas high levels of alpha3 and alpha5 integrin were expressed in MCF-7/ATCC cells. Inhibition of integrin function by a blocking antibody or inhibitory peptide diminished IGF-mediated motility in MCF-7/ATCC. In MCF-7/ATCC cells, IGF-I stimulation was associated with a movement of IRS-2 to the leading edge of filopodia. Thus, patterns of integrin expression among breast cancer cell lines may partially explain the different motility behavior of cells in response to IGF-I. IRS-2 activation and integrin occupancy are both required for IGF-stimulated motility.
Author List
Zhang X, Kamaraju S, Hakuno F, Kabuta T, Takahashi S, Sachdev D, Yee DAuthor
Sailaja Kamaraju MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Breast NeoplasmsCell Line, Tumor
Cell Movement
Female
Flow Cytometry
Humans
Immunoblotting
Insulin Receptor Substrate Proteins
Insulin-Like Growth Factor I
Integrins
Intracellular Signaling Peptides and Proteins
Phosphoproteins