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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.
Abstract:
The plasma membrane Ca(2+) ATPase (PMCA) is an essential regulator of free intracellular calcium. Recent studies have reported aberrant expression of the PMCA1 gene, a member of the PMCA family, in several cancer cell types. To elucidate the contribution of PMCA1 to oral carcinogenesis, we analyzed genetic and epigenetic changes and mRNA and protein expression in primary oral squamous cell carcinomas (OSCCs), oral premalignant lesions (OPLs), and OSCC-derived cell lines. The PMCA1 gene was epigenetically inactivated, but not mutated in the eight OSCC-derived cell lines tested. In clinical samples, frequent down-regulation of PMCA1 protein expression was found not only in primary OSCCs (43%), but also in OPLs (40%). Real-time quantitative reverse transcriptase-polymerase chain reaction data were consistent with the protein expression status. These results suggest that inactivation of the PMCA1 gene is a frequent and early event during oral carcinogenesis, and gene expression may be regulated by an epigenetic mechanism.
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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