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Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation

Jean-Charles Soria1, Ho-Young Lee, Janet I Lee

  • 1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 15, 2002
PubMed
Abstract

Insights

Loss of PTEN protein occurs in 24% of early-stage non-small cell lung cancer (NSCLC). Promoter methylation partially explains this PTEN silencing, highlighting its role in NSCLC development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • PTEN is a crucial tumor-suppressor gene located at chromosome 10q23.3.
  • PTEN inactivation, commonly via mutation or deletion, is observed in various human tumors.
  • Mechanisms like promoter methylation and translational modification can also lead to PTEN silencing.

Purpose of the Study:

  • To investigate PTEN protein expression in primary non-small cell lung cancer (NSCLC) samples.
  • To analyze PTEN promoter methylation status in NSCLC cell lines and primary tumors.

Main Methods:

  • PTEN expression was assessed using immunohistochemistry in 125 early-stage NSCLC patients.
  • PTEN promoter methylation was evaluated by methylation-specific PCR in 20 PTEN-negative primary tumors and 16 NSCLC cell lines.
  • Western and Northern blotting were employed to analyze PTEN expression in NSCLC cell lines.

Main Results:

  • A lack of PTEN staining was observed in 30 (24%) of 125 NSCLC specimens.
  • PTEN methylation was detected in 35% of PTEN-negative primary tumors and 69% of NSCLC cell lines.
  • PTEN methylation correlated significantly with PTEN expression (P = 0.025), and demethylation treatment increased PTEN mRNA.

Conclusions:

  • Loss of PTEN protein is a frequent event in early-stage NSCLC, despite rare genetic alterations.
  • Promoter methylation is a significant mechanism contributing to PTEN silencing in NSCLC.
  • These findings underscore the importance of PTEN in NSCLC pathogenesis.

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