Expression of SCC-S2, an Antiapoptotic Molecule, Correlates With Enhanced Proliferation and Tumorigenicity of MDA-MB 435 Cells

Oncogene. 2004 Jan 15;23(2):612-6. doi: 10.1038/sj.onc.1207123.

Abstract

SCC-S2/GG2-1/NDED is a recently discovered antiapoptotic molecule induced by the activation of the transcription factor NF-kappaB. Here we have examined a role of SCC-S2 in cell growth regulation in vitro and in vivo. Western blotting using an antipeptide antibody revealed endogenous SCC-S2 as a approximately 21 kDa cytosolic protein in human breast cancer cells (MDA-MB 231) and renal carcinoma cells (RCC-RS). The immunofluorescence detection method showed the cytosolic localization of FLAG-tagged human SCC-S2 in COS-1 transfectants. MDA-MB 435 human cancer cells stably transfected with the FLAG-tagged SCC-S2 cDNA exhibited increased growth rate as compared to control vector transfectants, as measured by the cell viability (>twofold; n=3; P<0.005) and thymidine-labeling procedures ( approximately sixfold; n=3; P<0.0001). SCC-S2 transfectants also displayed an increase in cell migration in collagen I as compared to control transfectants ( approximately twofold; n=3; P<0.005). In athymic mice, SCC-S2 transfectants showed significantly enhanced tumor growth as compared to control transfectants (mean tumor volumes, day 16: control, 56.86+/-19.82 mm(3); SCC-S2, 127.54+/-18.78 mm(3); n=5; P<0.03). The examination of a limited number of clinical specimens revealed higher expression levels of SCC-S2 protein in certain human tumor tissues as compared to the matched normal adjacent tissues. Taken together, the present studies demonstrate SCC-S2 as a novel oncogenic factor in cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • COS Cells
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology*
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Cell Transformation, Neoplastic*
  • Humans
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Proteins / genetics
  • Proteins / metabolism*
  • Transfection

Substances

  • GG2-1 protein, human
  • Proteins