Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression

Xihong Zhang, Sailaja Kamaraju, Fumihiko Hakuno, Tomohiro Kabuta, Shin Ichiro Takahashi, Deepali Sachdev, Douglas Yee

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 β1 integrin were detected in both strains of MCF-7. However, low levels of α5 and α3 were detected in MCF-7L cells whereas high levels of α3 and α5 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.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalBreast Cancer Research and Treatment
Volume83
Issue number2
DOIs
StatePublished - Jan 2004

Bibliographical note

Funding Information:
S.K. was supported by a fellowship grant from the Regis Breast Cancer Foundation. This work was supported by NIH Grant R01 CA74285 and PHS Cancer Center Support Grant P30 CA77398 (D.Y.).

Keywords

  • Insulin-like growth factor
  • Insulin-receptor substrate
  • Integrin
  • Motility
  • Proliferation

Fingerprint

Dive into the research topics of 'Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is associated with IRS-2 activation and integrin expression'. Together they form a unique fingerprint.

Cite this