Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 83, Issue 2, Pages 161-170Publisher
KLUWER ACADEMIC PUBL
DOI: 10.1023/B:BREA.0000010709.31256.c6
Keywords
insulin-like growth factor; insulin-receptor substrate; integrin; motility; proliferation
Categories
Funding
- NCI NIH HHS [R01 CA74285, P30 CA77398] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA074285, R01CA077398] Funding Source: NIH RePORTER
Ask authors/readers for more resources
In MCF-7L cells, insulin-like growth factor- (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 a3 and a5 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available