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The tetraspanin superfamily member NET-6 is a new tumor suppressor gene.

Publication ,  Journal Article
Huang, H; Sossey-Alaoui, K; Beachy, SH; Geradts, J
Published in: J Cancer Res Clin Oncol
October 2007

PURPOSE: NET-6 is a largely uncharacterized member of the tetraspanin superfamily. We have recently shown that its expression level was lowest in breast carcinomas with aggressive characteristics. We now describe the phenotypic and molecular changes induced in MDA-MB-231 breast carcinoma cells by ectopic NET-6 expression. METHODS: A GFP-NET-6 construct was transfected into very low expressing MDA-MB-231 cells. The subcellular distribution was studied by confocal microscopy. Cell proliferation in vitro was measured by MTT assay. Subcutaneous tumor formation in SCID mice was also studied. Other phenotypic parameters measured included growth in soft agar and extracellular matrix invasion. The effect of NET-6 transfection on the cell cycle was interrogated by flow cytometry. Deregulation of metalloproteinase expression was investigated by RT-PCR. Deregulation of proteins involved in apoptosis and cell cycle control was studied by Western blotting. RESULTS: Ectopic expression of NET-6 inhibited anchorage independent growth and invasion in a Boyden chamber assay. These effects were associated with downregulation of the matrix metalloproteinases MMP-1 and MMP-3. NET-6 had marked antiproliferative activity, both in vitro and in SCID mice. This effect was largely due to increased apoptosis. We identified upregulation of the pro-apoptotic molecules p53, bax, bak and caspase 3. CONCLUSIONS: Our data provide novel and compelling evidence that NET-6 is a potent new breast cancer suppressor gene.

Duke Scholars

Published In

J Cancer Res Clin Oncol

DOI

ISSN

0171-5216

Publication Date

October 2007

Volume

133

Issue

10

Start / End Page

761 / 769

Location

Germany

Related Subject Headings

  • Transfection
  • Tetraspanins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • Microscopy, Confocal
  • Mice, SCID
  • Mice
  • Membrane Proteins
  • Matrix Metalloproteinases
 

Citation

APA
Chicago
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MLA
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Huang, H., Sossey-Alaoui, K., Beachy, S. H., & Geradts, J. (2007). The tetraspanin superfamily member NET-6 is a new tumor suppressor gene. J Cancer Res Clin Oncol, 133(10), 761–769. https://doi.org/10.1007/s00432-007-0221-1
Huang, Huayi, Khalid Sossey-Alaoui, Sarah H. Beachy, and Joseph Geradts. “The tetraspanin superfamily member NET-6 is a new tumor suppressor gene.J Cancer Res Clin Oncol 133, no. 10 (October 2007): 761–69. https://doi.org/10.1007/s00432-007-0221-1.
Huang H, Sossey-Alaoui K, Beachy SH, Geradts J. The tetraspanin superfamily member NET-6 is a new tumor suppressor gene. J Cancer Res Clin Oncol. 2007 Oct;133(10):761–9.
Huang, Huayi, et al. “The tetraspanin superfamily member NET-6 is a new tumor suppressor gene.J Cancer Res Clin Oncol, vol. 133, no. 10, Oct. 2007, pp. 761–69. Pubmed, doi:10.1007/s00432-007-0221-1.
Huang H, Sossey-Alaoui K, Beachy SH, Geradts J. The tetraspanin superfamily member NET-6 is a new tumor suppressor gene. J Cancer Res Clin Oncol. 2007 Oct;133(10):761–769.
Journal cover image

Published In

J Cancer Res Clin Oncol

DOI

ISSN

0171-5216

Publication Date

October 2007

Volume

133

Issue

10

Start / End Page

761 / 769

Location

Germany

Related Subject Headings

  • Transfection
  • Tetraspanins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Oncology & Carcinogenesis
  • Neoplasm Invasiveness
  • Microscopy, Confocal
  • Mice, SCID
  • Mice
  • Membrane Proteins
  • Matrix Metalloproteinases