Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells

Yanhong Zhang, Quintin Pan, Hui Zhong, Sofia D. Merajver, Celina G. Kleer

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)R1080-R1089
JournalBreast cancer research : BCR
Volume7
Issue number6
StatePublished - 2005
Externally publishedYes

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Somatomedins
Breast
Epithelial Cells
Growth
Epithelial-Mesenchymal Transition
Inflammatory Breast Neoplasms
Somatomedin Receptors
Insulin Receptor Substrate Proteins
Insulin-Like Growth Factor Binding Proteins
Amino Acid Motifs
Small Interfering RNA
Intercellular Signaling Peptides and Proteins
Phosphorylation
Breast Neoplasms
Genes
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells. / Zhang, Yanhong; Pan, Quintin; Zhong, Hui; Merajver, Sofia D.; Kleer, Celina G.

In: Breast cancer research : BCR, Vol. 7, No. 6, 2005, p. R1080-R1089.

Research output: Contribution to journalArticle

Zhang, Yanhong ; Pan, Quintin ; Zhong, Hui ; Merajver, Sofia D. ; Kleer, Celina G. / Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells. In: Breast cancer research : BCR. 2005 ; Vol. 7, No. 6. pp. R1080-R1089.
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T1 - Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells

AU - Zhang, Yanhong

AU - Pan, Quintin

AU - Zhong, Hui

AU - Merajver, Sofia D.

AU - Kleer, Celina G.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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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