Overexpression of carbonic anhydrase-related protein XI promotes proliferation and invasion of gastrointestinal stromal tumors.
Three isoforms of carbonic anhydrase-related protein (CA-RP) are evolutionally well conserved among the CA gene family but lack classical CA activity. Although the biological function of CA-RPs is unknown, overexpression of CA-RP VIII has been reported in certain tumor types. Based on the finding that CA-RPs are commonly expressed in the neuronal cells, we investigated expression of all three CA-RPs in gastrointestinal stromal tumor (GIST). In contrast to no detectable signal of any of the three CA-RPs in intestinal cells of Cajal, immunohistochemical analysis showed distinct cytoplasmic expressions of CA-RPs VIII and XI in 13 (59%) and 20 (91%) of 22 GIST tissue specimens, respectively. The positive signals for both CA-RPs VIII and XI were more intense in the periphery than in the central part of GISTs, whereas no significant signal for CA-RP X expression was observed in any of the GISTs. These expression patterns of CA-RPs were consistently observed by reverse transcription-polymerase chain reaction-Southern blot and immunocytochemistry in the cultured GIST cell line GIST-T1. Ectopic expression of CA-RP XI in GIST-T1 cells induced cell proliferation and invasion in vitro. These findings indicate that CA-RP XI plays a role in the development of GIST.
Morimoto
Kaori
K
Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi, 783-8505, Japan. nisao@med.kochi-u.ac.jp
Nishimori
Isao
I
Takeuchi
Tamotsu
T
Kohsaki
Takuhiro
T
Okamoto
Nobuto
N
Taguchi
Takahiro
T
Yunoki
Shigeru
S
Watanabe
Ryohei
R
Ohtsuki
Yuji
Y
Onishi
Saburo
S
D014408:Biomarkers, Tumor / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000201:enzymology*; D049109:Cell Proliferation; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes; D009197:Myenteric Plexus / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000201:enzymology* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins
D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C512815:CA10 protein, human; C512817:CA11 protein, human; C512821:Car8 protein, mouse; C512818:CA8 protein, human; D047908:Intracellular Signaling Peptides and Proteins