A proapoptotic caspase recruitment domain protein gene, TMS1, is hypermethylated in human breast and gastric cancers.
BACKGROUND
Conway et al. demonstrated that methylation of the proapoptotic gene, TMS1, was observed in breast cancer cell lines and tissues, resulting in decreased TMS1 gene transcription. However, whether the TMS1 gene is hypermethylated in other cancers is uncertain.


METHODS
The expression of TMS1 mRNA was determined by quantitative RT-PCR. Methylation of the TMS1 gene was detected using methylation-specific PCR followed by bisulfite-modification of DNA.


RESULTS
Methylation of the TMS1 gene was observed in breast, gastric and colorectal cancer cells. Down-regulation of TMS1 gene transcription in colorectal cancer cells was restored by treatment with a demethylating agent. Methylation of the TMS1 gene was observed in 2 out of 19 breast cancer specimens and 1 out of 9 gastric cancers, but in none of 13 colorectal cancers.


CONCLUSIONS
These results suggest a direct role for aberrant methylation of the TMS1 gene in the progression of breast and gastric cancer involving down-regulation of the proapoptotic TMS1 gene.
Moriai
Ryosuke
R
Department of Clinical Laboratory Medicine and Division of Laboratory Diagnosis, Sapporo Medical University, School of Medicine, Sapporo, Japan.
Tsuji
Naoki
N
Kobayashi
Daisuke
D
Yagihashi
Atsuhito
A
Namiki
Yoshihisa
Y
Takahashi
Hiroshi
H
Watanabe
Naoki
N
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D053468:CARD Signaling Adaptor Proteins; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D019175:DNA Methylation; D000077209:Decitabine; D015536:Down-Regulation; D005629:Frozen Sections; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured
D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C402202:PYCARD protein, human; D011506:Proteins; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine