[HTML][HTML] Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells
Y Zhang, Q Pan, H Zhong, SD Merajver… - Breast Cancer Research, 2005 - Springer
Y Zhang, Q Pan, H Zhong, SD Merajver, CG Kleer
Breast Cancer Research, 2005•SpringerIntroduction CCN6/WISP3 belongs to the CCN (Cyr61, CTGF, Nov) family of genes that
contains a conserved insulin-like growth factor (IGF) binding protein motif. CCN6 is a
secreted protein lost in 80% of the aggressive inflammatory breast cancers, and can
decrease mammary tumor growth in vitro and in vivo. We hypothesized that inhibition of
CCN6 might result in the loss of a growth regulatory function that protects mammary
epithelial cells from the tumorigenic effects of growth factors, particularly IGF-1. Method We …
contains a conserved insulin-like growth factor (IGF) binding protein motif. CCN6 is a
secreted protein lost in 80% of the aggressive inflammatory breast cancers, and can
decrease mammary tumor growth in vitro and in vivo. We hypothesized that inhibition of
CCN6 might result in the loss of a growth regulatory function that protects mammary
epithelial cells from the tumorigenic effects of growth factors, particularly IGF-1. Method We …
Introduction
CCN6/WISP3 belongs to the CCN (Cyr61, CTGF, Nov) family of genes that contains a conserved insulin-like growth factor (IGF) binding protein motif. CCN6 is a secreted protein lost in 80% of the aggressive inflammatory breast cancers, and can decrease mammary tumor growth in vitro and in vivo. We hypothesized that inhibition of CCN6 might result in the loss of a growth regulatory function that protects mammary epithelial cells from the tumorigenic effects of growth factors, particularly IGF-1.
Method
We treated human mammary epithelial (HME) cells with a CCN6 hairpin short interfering RNA.
Results
CCN6-deficient cells showed increased motility and invasiveness, and developed features of epithelial-mesenchymal transition (EMT). Inhibition of CCN6 expression promoted anchorage-independent growth of HME cells and rendered them more responsive to the growth effects of IGF-1, which was coupled with the increased phosphorylation of IGF-1 receptor and insulin receptor substrate-1 (IRS-1).
Conclusion
Specific stable inhibition of CCN6 expression in HME cells induces EMT, promotes anchorage-independent growth, motility and invasiveness, and sensitizes mammary epithelial cells to the growth effects of IGF-1.
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