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See Latest ArticlesIncreased expression of both insulin receptor substrates 1 and 2 confers increased sensitivity to IGF-1 stimulated cell migration
Endocrine-Related Cancer, 06/05/09
De Blaquière GE et al. - In a study to determine if insulin receptor substrate-1 (IRS-1) is involved in, and to assess the contributions of IRS-1 and IRS-2 to, the migratory response of breast cancer cells to insulin-like growth factors (IGFs), it appears that both IRS-1 and IRS-2 control the migratory response of breast cancer cells to IGF-1 and may be key molecules in determining breast cancer spread.
Methods- The purpose was to determine if IRS-1 is involved in, and to assess the contributions of IRS-1 and IRS-2 to, the migratory response of breast cancer cells to IGFs.
- Expression of IRS-1 and IRS-2 varied considerably between 10 breast cancer cell lines.
- Oestrogen increases expression of the type I IGF receptor, IRS-1 and IRS-2 in MCF-7 and ZR-75 cells.
- Oestrogens may control the sensitivity of breast cancer cells to IGFs by regulating expression of components of the IGF signal transduction pathway.
- The migratory response to a range of IGF-1 concentrations was measured in MCF-7 and MDA-MB-231 breast cancer cells in which IRS-1 and IRS-2 levels were modulated using a doxycycline-inducible expression system.
- Induction of both IRS-1 and IRS-2 expression increased the sensitivity of the migratory response to IGF-1 but did not increase the magnitude of the response stimulated at higher concentrations of IGF-1.
- Knockdown of IRS-1, IRS-2, and the type I IGF receptor in MCF-7 and MDA-MB-2231 cells decreased sensitivity to IGF-1.
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