[The role of MN/CA IX antigen in carcinogenesis and metastasis of renal cell carcinoma].
MN/CA IX is a carbonic anhydrase (CA) isoenzyme expressed in normal alimentary tract in a tissue-specific manner. This antigen is activated in the majority of renal cell carcinomas (RCC) but not in normal kidney tissues. Although the exact role of CA activity in carcinogenesis and metastasis has not been established, MN/CA9 has been suggested to be implicated in acidification of extracellular milieu surrounding the cancer cells and thus create a microenvironment conductive to tumor growth and spread. Mutations in the von Hippel-Lindau (VHL) gene cause the familial syndrome and are also found in the majority of sporadic RCC. Wild-type VHL was recently described to down-regulate MN/CA9 in RCC cell lines, and the molecular mechanism of MN/CA9 and VHL in renal carcinogenesis is of interest. To investigate the mechanism of MN/CA9 activation in RCC, we examined the methylation status of this gene in RCC cell lines and human tissue samples and found that hypomethylation in the promoter region may play an important role in the expression of MN/CA9. RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cells in the blood. This antigen may be a potential therapeutic target as well as diagnostic marker for RCC. Therefore, we are currently investigating whether or not MN/CA IX peptide could be an appropriate molecule for use antigen specific immunotherapy on RCC patients.
Nakagawa
Y
Y
Department of Urology, Nara Medical University.
Uemura
H
H
Shimizu
K
K
Cho
M
M
Yoshikawa
M
M
Hirao
Y
Y
Yoshikawa
K
K
D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D002292:Carcinoma, Renal Cell / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology
D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases