Activation of Alternative Wnt Signaling Pathways in Human Mammary Gland and Breast Cancer Cells
Annual summary 1 Jun 2003-31 May 2004
COLUMBIA UNIV NEW YORK
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Several of the Wnt genes family are expressed and differentially regulated during breast development. The Wnt signal transduction pathway has been implicated in mammary tumorigenesis in different species as well as in human breast cancer cell lines. The various Wnt family members can exert differential effects on the growth and morphogenesis of mammary epithelial cells, while some Wnts are strongly transforming factors, others show weak or directly no transforming effect at all. Wnts are known to activate several different signaling pathways through the same receptor and thereby elicit unique cellular responses. These pathways include the canonical 3-cateninTcfLef, as well as the activation of small Rho GTPases guanosine-triphosphatases and INK c-Jun NH2-terminal kinase signaling. This WntFrizzled pathway appears to employ Dvl to stimulate RhoA and RacINK activities and is likely mediated by independent Dvl- RhoA and Dvl-Rac complexes induced upon Wnt signaling Habas et al., 2001. There are clear evidences of a role of canonical Wnt signaling in breast cancer Howe et al., 2004 Hatsell et al., 2003, and in light that a canonical Wnt like Wnt-l can also upregulate non canonical signaling, its role in breast cancer cells needs to be further investigated.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research