Plasma membrane Ca2+ ATPase isoform 1 down-regulated in human oral cancer

Kengo Saito1, Katsuhiro Uzawa, Yosuke Endo

  • 1Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Japan.

Oncology Reports
|December 6, 2005
PubMed

Insights

The plasma membrane calcium ATPase 1 (PMCA1) gene is frequently inactivated early in oral cancer development, primarily through epigenetic silencing rather than mutation. This down-regulation occurs in both premalignant lesions and oral squamous cell carcinomas.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Plasma membrane calcium ATPase (PMCA) regulates intracellular calcium levels.
  • Aberrant PMCA1 gene expression is observed in various cancer types.
  • PMCA1's role in oral carcinogenesis requires elucidation.

Purpose of the Study:

  • To investigate the genetic and epigenetic alterations of PMCA1 in oral squamous cell carcinoma (OSCC).
  • To analyze PMCA1 mRNA and protein expression in oral premalignant lesions (OPLs) and OSCC.
  • To determine the contribution of PMCA1 to oral carcinogenesis.

Main Methods:

  • Analysis of genetic and epigenetic changes in OSCC cell lines and clinical samples.
  • Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for mRNA expression.
  • Western blotting or immunohistochemistry for protein expression analysis.

Main Results:

  • PMCA1 gene was epigenetically inactivated, not mutated, in OSCC cell lines.
  • Down-regulation of PMCA1 protein expression was frequent in primary OSCC (43%) and OPLs (40%).
  • mRNA expression levels correlated with protein expression, supporting gene silencing.

Conclusions:

  • PMCA1 gene inactivation is a frequent and early event in oral carcinogenesis.
  • Epigenetic mechanisms, specifically silencing, likely regulate PMCA1 expression.
  • PMCA1 down-regulation may serve as an early biomarker for oral cancer development.

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