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LRRC3B gene is frequently epigenetically inactivated in several epithelial malignancies and inhibits cell growth and

Klas Haraldson1, Vladimir I Kashuba, Alexey A Dmitriev

  • 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.

Biochimie
|February 11, 2012
PubMed

Insights

The LRRC3B gene is frequently methylated or deleted in multiple epithelial cancers, suggesting its role as a tumor suppressor. Down-regulation and growth inhibition were observed, supporting its involvement in carcinogenesis.

Area of Science:

  • Genetics
  • Oncology
  • Molecular Biology

Background:

  • Alterations in chromosome 3 are common in epithelial cancers.
  • The LRRC3B gene's role in carcinogenesis is largely unexplored.

Purpose of the Study:

  • To investigate the frequency of methylation and deletion of LRRC3B in various epithelial cancers.
  • To determine the functional impact of LRRC3B alterations on gene expression and cell growth.

Main Methods:

  • NotI microarrays hybridized with tumor/normal samples from breast, lung, cervical, kidney, colon, ovarian, and prostate cancers.
  • Bisulfite sequencing to confirm methylation.
  • RT-qPCR for expression analysis.
  • In vitro colony formation assays to assess growth inhibition.

Main Results:

  • LRRC3B was frequently methylated and/or deleted across all tested epithelial cancers, with specific frequencies noted for each type.
  • Methylation was confirmed by bisulfite sequencing.
  • LRRC3B expression was down-regulated in late-stage renal cell carcinoma and ovarian cancers.
  • LRRC3B demonstrated significant cell growth inhibitory activity in vitro.

Conclusions:

  • LRRC3B alterations (methylation/deletion) are prevalent in epithelial cancers.
  • LRRC3B down-regulation and its growth-inhibitory function suggest it acts as a tumor suppressor gene.
  • LRRC3B may play a significant role in the process of carcinogenesis.

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