Expression of MAGE genes in human colorectal carcinoma.
OBJECTIVE
The human genes MAGE-1 and -3 encode tumor-specific peptide antigens, which are recognized by autologous cytotoxic T lymphocytes. The antigens coded by those genes may be useful for cancer immunotherapy. There is, however, little information on the expression of these genes in human colorectal carcinomas.


METHODS
The expression of MAGE-1, -2, and -3 genes in 54 pairs of tumor and corresponding normal tissue specimens of the colorectum was determined by means of reverse transcription polymerase chain reaction. The induction of MAGE-1, -2, -3, and -4 gene expression in eight colorectal carcinoma cell lines also was examined by use of a demethylating agent, 5-Aza-2'-deoxycytidine (DAC).


RESULTS
The expression of MAGE genes was not recognized in normal colorectal tissues at all. In tumor tissue specimens, the expression of MAGE-1, -2, and -3 was recognized in 16 (30%), 15 (28%), and 11 (20%) patients, respectively. The expression was seen frequently in patients with liver metastasis (p < 0.01). Although MAGE-1 or -3 genes were not induced by DAC, MAGE-2 or -4 genes were induced in three of four MAGE-2 negative cell lines or three of seven MAGE-4 negative cell lines, respectively.


CONCLUSIONS
The MAGE genes were expressed exclusively in tumor tissues of one third of patients with colorectal carcinoma. The identification of such tumor rejection antigens is considered to uncover a new possibility for the specific immunotherapy of colorectal carcinoma. The demethylating agent may increase the number of patients who might be candidates for MAGE-specific immunotherapy.
Mori
M
M
Department of Surgery, Kyushu University, Beppu, Japan.
Inoue
H
H
Mimori
K
K
Shibuta
K
K
Baba
K
K
Nakashima
H
H
Haraguchi
M
M
Tsuji
K
K
Ueo
H
H
Barnard
G F
GF
Akiyoshi
T
T
D000951:Antigens, Neoplasm / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; C072012:MAGEB2 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D000077209:Decitabine; D001374:Azacitidine