Plasma membrane Ca2+ ATPase isoform 1 down-regulated in human oral cancer.
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.
Saito
Kengo
K
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Japan.
Uzawa
Katsuhiro
K
Endo
Yosuke
Y
Kato
Yoshikuni
Y
Nakashima
Dai
D
Ogawara
Katsunori
K
Shiba
Masashi
M
Bukawa
Hiroki
H
Yokoe
Hidetaka
H
Tanzawa
Hideki
H
D000252:Calcium-Transporting ATPases / Q000032:analysis / Q000235:genetics*; D027682:Cation Transport Proteins / Q000032:analysis / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009062:Mouth Neoplasms / Q000737:chemistry / Q000235:genetics*; D053499:Plasma Membrane Calcium-Transporting ATPases; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
C506952:ATP2B1 protein, human; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases