WISP3 is a novel tumor suppressor gene of inflammatory breast cancer

Kleer, Celina G.; Zhang, Yanhong; Pan, Quintin; Golen, Kenneth L. van; Wu, Zhi Fen; Livant, Donna L.; Merajver, Sofía D.

doi:10.1038/sj.onc.1205462

Cited by 134 publications

(127 citation statements)

References 22 publications

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“…For example, we found changes in gene expression and networks for BAX and IL1B which are pro-apoptotic and pro-inflammatory response genes, respectively [29][30]. In addition, clustering analyses between LFS and WT samples highlighted WISP3 which is an anti-inflammatory response gene which help prolong cell growth and survival [31]. Other significant genes in the analyses included CDK2, CDKN1A (p21), and CHEK1, all regulators of the cell cycle [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers

et al. 2010

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AbstrAct:Specific changes in gene expression during cancer initiation should enable discovery of biomarkers for risk assessment, early detection and targets for chemoprevention. It has been previously demonstrated that altered mRNA and proteome signatures of morphologically normal cells bearing a single inherited "hit" in a tumor suppressor gene parallel many changes observed in the corresponding sporadic cancer. Here, we report on the global gene expression profile of morphologically normal, cultured primary breast epithelial and stromal cells from Li-Fraumeni syndrome (LFS) TP53 mutation carriers. Our analyses identified multiple changes in gene expression in both morphologically normal breast epithelial and stromal cells associated with TP53 haploinsufficiency, as well as interlocking pathways. Notably, a dysregulated p53 signaling pathway was readily detectable. Pharmacological intervention with the p53 rescue compounds CP-31398 and PRIMA-1 provided further evidence in support of the central role of p53 in affecting these changes in LFS cells and treatment for this cancer. Because loss of signaling mediated by TP53 is associated with the development and survival of many human tumors, identification of gene expression profiles in morphologically normal cells that carry "one-hit" p53 mutations may reveal novel biomarkers, enabling the discovery of potential targets for chemoprevention of sporadic tumors as well.

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Section: Discussionmentioning

confidence: 99%

A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers

et al. 2010

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“…Therefore, downregulation of WISP-1 by MRP-1/CD9 gene transduction might lead to less aggressive tumor behavior. However, the exact biological function of WISP-3 is still unclear because it has also been reported to be a tumor suppressor gene (Kleer et al, 2002). c-Myc is an oncogenic transcription factor that integrates the cell-cycle machinery, cellular metabolism, and the apoptotic pathways (Dang et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

MRP-1/CD9 gene transduction downregulates Wnt signal pathways

et al. 2004

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Motility-related protein-1 (MRP-1/CD9) is a transmembrane glycoprotein that has been implicated in cell adhesion, motility, proliferation, and differentiation. It has a functional role as a tumor metastatic suppressor. During tumor progression, a reduction of MRP-1/CD9 gene expression results in tumor cells with a high metastatic potential. However, the mechanism of action of MRP-1/CD9 is still unclear. We studied changes of gene expression in relation to MRP-1/CD9 gene transduction into tumor cell lines, HT1080 and A549, using microarray assays and real-time PCR. Consequently, we have demonstrated that MRP-1/ CD9 gene transduction can downregulate expression of several Wnt family genes, such as Wnt1, Wnt2b1 and Wnt5a, and their target genes, including WISP-1 (Wnt-1 induced secreted protein 1), WISP-3, c-Myc, vascular endothelial growth factor-A, and matrix metalloproteinase-26. Western blot analyses also showed that MRP-1/CD9 gene transduction downregulated expression of Wnt1 protein and its target proteins. In addition, a neutralizing anti-MRP-1/CD9 monoclonal antibody inhibited the downregulation of Wnt signal pathways in MRP-1/CD9-transfected cells. The present study has revealed that the MRP-1/CD9 signal is located upstream of the Wnt signal pathways. Therefore, MRP-1/CD9 could suppress cell transformation including epithelial to mesenchymal transition through downregulation of Wnt1, and might suppress tumor metastasis through downregulation of Wnt5a.

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“…At molecular level, overexpression of RhoC GTPase and loss of WISP3 is linked to breast tumours from patients with IBC (Van Golen et al, 1999;Kleer et al 2002). At biological level, increased angiogenesis in breast tumours from patients with IBC was demonstrated in several independent studies (Colpaert et al, 2003;Van der Auwera et al, 2004).…”

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confidence: 99%

Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

et al. 2007

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The present study aims at a platform-independent confirmation of previously obtained cDNA microarray results on inflammatory breast cancer (IBC) using Affymetrix chips. Gene-expression data of 19 IBC and 40 non-IBC specimens were subjected to clustering and principal component analysis. The performance of a previously identified IBC signature was tested using clustering and gene set enrichment analysis. The presence of different cell-of-origin subtypes in IBC was investigated and confirmed using immunohistochemistry on a TMA. Differential gene expression was analysed using SAM and topGO was used to identify the fingerprints of a pro-metastatic-signalling pathway. IBC and non-IBC have distinct gene-expression profiles. The differences in gene expression between IBC and non-IBC are captured within an IBC signature, identified in a platform-independent manner. Part of the gene-expression differences between IBC and non-IBC are attributable to the differential presence of the cell-of-origin subtypes, since IBC primarily segregated into the basal-like or ErbB2-overexpressing group. Strikingly, IBC tumour samples more closely resemble the gene-expression profile of T1/T2 tumours than the gene-expression profile or T3/T4 tumours. We identified the insulin-like growth factor-signalling pathway, potentially contributing to the biology of IBC. Our previous results have been validated in a platform-independent manner. The distinct biological behaviour of IBC is reflected in a distinct gene-expression profile. The fact that IBC tumours are quickly arising tumours might explain the close resemblance of the IBC gene-expression profile to the expression profile of T1/T2 tumours.

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WISP3 is a novel tumor suppressor gene of inflammatory breast cancer

Cited by 134 publications

References 22 publications

A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers

A molecular signature of normal breast epithelial and stromal cells from Li-Fraumeni syndrome mutation carriers

MRP-1/CD9 gene transduction downregulates Wnt signal pathways

Distinct molecular phenotype of inflammatory breast cancer compared to non-inflammatory breast cancer using Affymetrix-based genome-wide gene-expression analysis

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