Insulin-like Growth Factor-1 (IGF-1) Induces WISP-2/CCN5 via Multiple Molecular Cross-talks and Is Essential for Mitogenic Switch by IGF-1 Axis in Estrogen Receptor–Positive Breast Tumor Cells

Dhar, Kakali; Banerjee, Snigdha; Dhar, Gopal; Sengupta, Krishanu

doi:10.1158/0008-5472.can-06-3753

Cited by 36 publications

(50 citation statements)

References 52 publications

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“…CCN5/WISP-2 specific shRNAs or mismatched shRNA were designed, synthesized, and cloned into the pSilencer vectors according to our previous method (7,27). RNA interference sequences for CCN5/WISP-2 were described in details earlier (6)(7)(8).…”

Section: Methodsmentioning

confidence: 99%

“…For transient transfection experiments, breast tumor cells were transfected with shRNAs or expression vectors (i.e., pCMV) containing missense mutant p53 genes (R-175H or R-273H; kindly provided by Bert Vogelstein) using Lipofectin reagent (Invitrogen) according to our previous method (7,27).…”

Section: Methodsmentioning

confidence: 99%

“…Cytoplasmic RNA was extracted from cells using Trizol (Invitrogen) extraction procedure as described previously (7,27,28). cDNA preparation, reverse transcription-PCR analysis, and nonradioactive probe synthesis were performed essentially as reported (7,29).…”

Section: Methodsmentioning

confidence: 99%

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Gain of Oncogenic Function of p53 Mutants Induces Invasive Phenotypes in Human Breast Cancer Cells by Silencing CCN5/WISP-2

et al. 2008

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CCN5/WISP-2 is overexpressed in noninvasive breast cancer cells and tissue samples, whereas its expression is minimal or undetected in invasive conditions. CCN5/WISP-2 has been considered as an antiinvasive gene because CCN5/WISP-2 silencing augments the invasive phenotypes in vitro. However, the mechanism of silencing of CCN5 during the progression of the disease has been elusive. Because p53 mutations are associated with breast cancer progression and have been shown to correlate inversely with CCN5/WISP-2 expression in other cancer cell types, the objective of this study was to explore whether p53 mutants suppress CCN5 expression in breast tumor cells resulting in the progression of this disease. We found CCN5 expression is inversely correlated with the mutational activation of p53 in human breast tumor cells. The ectopic expression of p53 mutants in ER-positive noninvasive breast tumor cells silenced the CCN5/WISP-2 expression and enhanced invasive phenotypes, including the induction of morphologic changes from the epithelial-to-mesenchymal type along with the alterations of hallmark proteins of these cell types and an augmentation of the migration of these cells. The suppression of CCN5 by the p53 mutants can be nullified by estrogen signaling in these cells through the transcriptional activation of the CCN5 gene. Moreover, the invasive changes can be imitated by blocking the CCN5/WISP-2 expression through RNA interference or can be reversed by the addition of CCN5/WISP-2 recombinant protein in the culture. Thus, these studies suggest that CCN5 inactivation could be an essential molecular event for p53 mutant-induced invasive phenotypes. [Cancer Res 2008;68(12):4580-7]

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Gain of Oncogenic Function of p53 Mutants Induces Invasive Phenotypes in Human Breast Cancer Cells by Silencing CCN5/WISP-2

et al. 2008

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“…The ability of EGF, PMA, or IGF-1 alone to induce MCF-7 cell proliferation was abrogated by CCN5 knockdown (Banerjee et al 2005;Dhar et al 2007b;Sengupta et al 2006). Similarly, Tip30 −/− mammary epithelial cells were shown to have reduced proliferation in response to serum after CCN5 knockdown (Pecha et al 2007).…”

Section: Proliferationmentioning

confidence: 95%

CCN5: biology and pathophysiology

Russo

Castellot

2010

Journal of Cell Communication and Signaling

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CCN5 is one of six proteins in the CCN family. This family of proteins has been shown to play important roles in many processes, including proliferation, migration, adhesion, extracellular matrix regulation, angiogenesis, tumorigenesis, fibrosis, and implantation. In this review, we focus on the biological and putative pathophysiological roles of CCN5. This intriguing protein is structurally unique among the CCN family members, and has a unique biological activity profile as well.

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“…CCN5 has both growth-promoting and growth-arresting competence depending on cell types and the microenvironment of the cells. For example, overproduction of CCN5 by epidermal growth factor or IGF-I is required for the mitogenic action of these growth factors in estrogen receptor-positive (ER + ), noninvasive breast tumor cells (9)(10)(11), whereas it acts as a growth arrest-specific gene in vascular smooth muscle cells and prostate cancer cells (12). In addition, it is most likely that CCN5 plays a preventive role in the progression of pancreatic cancer as it participates in morphologic alterations from mesenchymal to epithelial transition of pancreatic adenocarcinoma cells (13).…”

Section: Introductionmentioning

confidence: 99%

CCN5/WISP-2 Expression in Breast Adenocarcinoma Is Associated with Less Frequent Progression of the Disease and Suppresses the Invasive Phenotypes of Tumor Cells

et al. 2008

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Although previous in vitro studies predicted that CCN5/ WISP-2 may act as an anti-invasive gene in breast cancer, the distribution pattern of CCN5 in breast cancer samples is conflicting. Thus, we systematically investigated the CCN5 expression profile in noninvasive and invasive breast tumor samples and its functional relevance in breast cancer progression. The studies showed that CCN5 expression is biphasic, such that in normal samples CCN5 expression is undetectable, whereas its expression is markedly increased in noninvasive breast lesions, including atypical ductal hyperplasia and ductal carcinoma in situ. Further, CCN5 mRNA and protein levels are significantly reduced as the cancer progresses from a noninvasive to invasive type. Additionally, we showed that CCN5 mRNA and protein level was almost undetectable in poorly differentiated cancers compared with the moderately or well-differentiated samples and its expression inversely correlated with lymph node positivity. The result was further supported by evaluating the RNA expression profile in microdissected sections using real-time PCR analysis. Therefore, our data suggest a protective function of CCN5 in noninvasive breast tumor cells. This hypothesis was further supported by our in vitro studies illuminating that CCN5 is a negative regulator of migration and invasion of breast cancer cells, and these events could be regulated by CCN5 through the modulation of the expression of genes essential for an invasive front. These include Snail-E-cadherin signaling and matrix metalloproteinase (MMP)-9 and MMP-2. Collectively, these studies suggest that the protective effect of CCN5 in breast cancer progression may have important therapeutic implications. [Cancer Res 2008;68(18):7606-12]

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Insulin-like Growth Factor-1 (IGF-1) Induces WISP-2/CCN5 via Multiple Molecular Cross-talks and Is Essential for Mitogenic Switch by IGF-1 Axis in Estrogen Receptor–Positive Breast Tumor Cells

Cited by 36 publications

References 52 publications

Gain of Oncogenic Function of p53 Mutants Induces Invasive Phenotypes in Human Breast Cancer Cells by Silencing CCN5/WISP-2

Gain of Oncogenic Function of p53 Mutants Induces Invasive Phenotypes in Human Breast Cancer Cells by Silencing CCN5/WISP-2

CCN5: biology and pathophysiology

CCN5/WISP-2 Expression in Breast Adenocarcinoma Is Associated with Less Frequent Progression of the Disease and Suppresses the Invasive Phenotypes of Tumor Cells

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