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The amplified WWP1 gene is a potential molecular target in breast cancer

Ceshi Chen1, Zhongmei Zhou, Jeffrey S Ross

  • 1The Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA. chenc@mail.amc.edu

International Journal of Cancer
|March 3, 2007
PubMed

Insights

Genomic aberrations of WWP1, a gene on chromosome 8q21, are common in breast cancer. WWP1 overexpression promotes cancer cell proliferation and inhibits tumor suppression, suggesting its role in breast cancer development.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Amplification of chromosome 8q21 is frequent in breast cancer.
  • WWP1, a ubiquitin E3 ligase in the 8q21 region, negatively regulates the TGF-beta tumor suppressor pathway.

Purpose of the Study:

  • To investigate the role of WWP1 in breast cancer pathogenesis.
  • To analyze WWP1 gene dosage, expression, and function in breast cancer.

Main Methods:

  • Analysis of WWP1 gene copy number and mRNA expression using real-time RT-PCR, Northern blot, and Western blot.
  • RNA interference (RNAi)-mediated WWP1 knockdown in breast cancer cell lines (MCF7, HCC1500).
  • Overexpression of WWP1 in immortalized breast epithelial cell lines (MCF10A, 184B5) using a lentiviral system.

Main Results:

  • WWP1 copy number gain observed in 51% of cell lines and 41% of primary tumors.
  • WWP1 mRNA up-regulation in 58% of cell lines and significantly higher expression in tumors versus normal tissues.
  • WWP1 knockdown induced cell growth arrest and apoptosis, while overexpression promoted proliferation.

Conclusions:

  • Genomic aberrations and overexpression of WWP1 are implicated in breast cancer.
  • WWP1 plays a functional role in promoting breast cancer cell proliferation and potentially inhibiting tumor suppressor pathways.

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