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Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumours

World Journal of Gastroenterology 2005年第2期11卷 155-163页

作者： Antti J. Kivel Jyrki Kivel juha saarnio Seppo Parkkila Department of Anatomy and Cell Biology University of OuluFinland Institute of Medical TechnologyUniversity of Tampere and Tampere University HospitalFinland Institute of Dentistry University of HelsinkiFinlandResearch Institute of Military MedicineCentral Military HospitalHelsinkiFinland Department of Surgery University of OuluFinland Institute of Medical Technology University of Tampere and Tampere University HospitalFinland Department of Clinical ChemistryUniversity of OuluFinland

Carbonic anhydrases (CAs) catalyse the hydration of C02 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membrane-bound isoenzymes IX and XII have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.

关键词： Gastrointestinal tract Gastrointestinal tumour Carbonic anhydrases

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Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases IX and XII in normal and neoplastic colorectal mucosa

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World Journal of Gastroenterology 2005年第17期11卷 2616-2625页

作者： Antti J. Kivela Seppo Parkkila juha saarnio Tuomo J. Karttunen Jyrki Kivela Anna-Kaisa Parkkila Maria Bartosova Vojtech Mucha Michal Novak Abdul Waheed William S. Sly Hannu Rajaniemi Silvia Pastorekova Jaromir Pastorek Department of Anatomy and Cell Biology University of Oulu Finland Institute of Medical Technology University of Tampere and Tampere University Hospital Finland Department of Surgery University of Oulu Finland Department of Pathology University of Oulu Finland Institute of Dentistry University of Helsinki and Central Military Hospital Finland Department of Neurology Tampere University Hospital Finland Center of Molecular Medicine Institute of Virology Slovak Academy of SciencesBratislavaSlovak Republic Institute of Neuroimmunology Slovak Academy of Sciences BratislavaSlovak Republic Edward A. Doisy Department of Biochemistry and Molecular Biology Saint Louis University School of Medicine Missouri

AIM:To analyze possible relationships between CA IX/ CA XII and pVHL expression in normal and neoplastic colorectal mucosa. METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA IX, CA XII and pVHL. VHL mRNAs from 14 fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and G412mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGFas an indicator of hypoxia that uncouples the pVHL control. RESULTS: Tumor tissues were associated with a borderline increase of CA IX staining signal and slight but significant decrease of CA XII immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL and CA IX/CA XII proteins as well as between MEGFand CA9 mRNAs, but the tumor-associated changes in mRNA levels of VEGFand CA12 showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA IX/CA XII and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA IX/CA XII in colorectal tumors seems rather complex and is not evident merely at the expression levels.

关键词： Carbonic anhydrase VHL VEGF Colorectal cancer

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