 | CELL AND MOLECULAR BIOLOGY OF PANCREATIC CARCINOMA: RECENT DEVELOPMENTS IN RESEARCH AND EXPERIMENTAL THERAPY
Copyright © 1999 by the New York Academy of Sciences
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Annals of the New York Academy of Sciences 880:5-16 (1999)
© 1999 New York Academy of Sciences
Carbonic Anhydrase in Human Pancreas: Hypotheses for the Pathophysiological Roles of CA Isozymes
ISAO NISHIMORIa,c,
KIYOMI FUJIKAWA-ADACHIa,
SABURO ONISHIa AND
MICHAEL A. HOLLINGSWORTHb
aFirst Department of Internal Medicine, Kochi Medical School, Kochi 783-8505, Japan
bEppley Cancer Institute, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
cCorresponding author: Isao Nishimori, M. D., Ph.D., First Department of Internal Medicine, Kochi Medical School, Nankoku, Kochi 783-8505, Japan. Phone and fax +81 888-80-2338: e-mail, nisao{at}kochi-ms.ac.jp
Among more than ten isozymes of the carbonic anhydrase (CA) family, only cytoplasmic CA II and membrane-bound CA IX have been reported to be expressed in human pancreas. To study the mRNA expression of CA isozymes in human pancreas, reverse transcriptase-polymerase chain reaction (RT-PCR)-Southern blot analysis and cDNA sequencing following RT-PCR were employed. CA II, IV, VI, IX, and XII were clearly identified in polyA+ RNA from normal human pancreas by RT-PCR-Southern blotting. Results with cultured pancreatic tumor cell lines suggest that CA II, IV, IX, and XII are expressed in the ductal cells, and CA VI is expressed in the acinar cells. We propose a hypothesis for the pathophysiological function of CA isozymes in human pancreas; (1) the intraluminal CA isozymes (CA IV, VI, and possibly XII) form a mutually complementary system with cytoplasmic CA II to regulate the luminal pH of the pancreatic duct system and work as a self-defense mechanism against pancreatitis; (2) CA II and other CA isozymes play a pathological role in the autoimmune process of idiopathic chronic pancreatitis.
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