WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer.

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  • Author(s): Kleer CG;Kleer CG; Zhang Y; Pan Q; Gallagher G; Wu M; Wu ZF; Merajver SD
  • Source:
    Breast cancer research : BCR [Breast Cancer Res] 2004; Vol. 6 (1), pp. R110-5.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100927353 Publication Model: Print Cited Medium: Internet ISSN: 1465-542X (Electronic) Linking ISSN: 14655411 NLM ISO Abbreviation: Breast Cancer Res Subsets: MEDLINE
    • Publication Information:
      Publication: London, UK : BioMed Central Ltd
      Original Publication: London, UK : Current Science, c1999-
    • Subject Terms:
      Breast Neoplasms/*pathology ; Insulin-Like Growth Factor Binding Proteins/*genetics ; Neoplasm Proteins/*genetics ; rho GTP-Binding Proteins/*genetics; Blotting, Western ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; CCN Intercellular Signaling Proteins ; Cell Division/genetics ; Cell Division/physiology ; Cell Line ; Cell Line, Tumor ; DNA, Antisense/genetics ; Humans ; Inflammation ; Insulin-Like Growth Factor Binding Proteins/metabolism ; Neoplasm Proteins/metabolism ; Plasmids/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Transfection ; Vascular Endothelial Growth Factor A/metabolism ; rho GTP-Binding Proteins/metabolism ; rhoC GTP-Binding Protein
    • Abstract:
      Background: Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer. We found concordant and consistent alterations of two genes in 90% of IBC tumors when compared to stage matched, non-IBC tumors: overexpression of RhoC GTPase and loss of WISP3. Further work revealed that RhoC is a transforming oncogene for HME cells. Despite the aggressiveness of the RhoC-driven phenotype, it does not quantitatively reach that of the true IBC tumors. We have demonstrated that WISP3 has tumor growth and angiogenesis inhibitory functions in IBC. We hypothesized that RhoC and WISP3 cooperate in the development of IBC.
      Methods: Using an antisense approach, we blocked WISP3 expression in HME cells (HME/AS WISP3). Cellular proliferation and anchorage independent growth were determined using the MTT assay and the anchorage independent growth in soft agar assay. VEGF was measured in the conditioned media of the HME/ AS WISP3 by ELISA.
      Results: Antisense inhibition of WISP3 expression in HME cells increased the levels of RhoC mRNA and increased cellular proliferation, anchorage independent growth and secretion of VEGF in these cells. Conversely, restoration of WISP3 expression in the highly malignant IBC cell line SUM149 was able to decrease the expression of RhoC protein.
      Conclusion: WISP3 modulates RhoC expression in HME cells and in the IBC cell line SUM149, and provide further evidence in support that these two genes act in concert to give rise to the highly aggressive IBC phenotype. We propose a model of this interaction as a starting point for further investigations.
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    • Grant Information:
      K08CA090876-01A2 United States CA NCI NIH HHS; R01 CA077612 United States CA NCI NIH HHS; P30 CA046592 United States CA NCI NIH HHS; M01-RR00042 United States RR NCRR NIH HHS; R01CA77612 United States CA NCI NIH HHS; P30CA46592 United States CA NCI NIH HHS; M01 RR000042 United States RR NCRR NIH HHS; K08 CA090876 United States CA NCI NIH HHS
    • Accession Number:
      0 (CCN Intercellular Signaling Proteins)
      0 (CCN6 protein, human)
      0 (DNA, Antisense)
      0 (Insulin-Like Growth Factor Binding Proteins)
      0 (Neoplasm Proteins)
      0 (RNA, Messenger)
      0 (Vascular Endothelial Growth Factor A)
      EC 3.6.5.2 (RHOC protein, human)
      EC 3.6.5.2 (rho GTP-Binding Proteins)
      EC 3.6.5.2 (rhoC GTP-Binding Protein)
    • Publication Date:
      Date Created: 20031231 Date Completed: 20040108 Latest Revision: 20191108
    • Publication Date:
      20240829
    • Accession Number:
      PMC400654
    • Accession Number:
      10.1186/bcr755
    • Accession Number:
      14696649