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Down-Regulation of Transmembrane Carbonic Anhydrases in Renal Cell Carcinoma Cell Lines By Wild-Type Von-Hippel-Lindau Transgenes

  1. Author:
    Ivanov, S. V.
    Kuzmin, I.
    Wei, M. H.
    Pack, S.
    Geil, L.
    Johnson, B. E.
    Stanbridge, E. J.
    Lerman, M. I.

  2. Author Address

    Ivanov SV SCI APPLICAT INT CORP FREDERICK IMMUNOL LAB INTRAMURAL RES SUPPORT PROGRAM FREDERICK, MD 21702 USA NCI FREDERICK CANC RES & DEV CTR IMMUNOBIOL LAB FREDERICK, MD 21702 USA NCI PATHOL LAB NIH BETHESDA, MD 20889 USA NCI MED BRANCH NIH BETHESDA, MD 20892 USA UNIV CALIF IRVINE COLL MED DEPT MICROBIOL & MOL GENET IRVINE, CA 92717 USA
    1. Year: 1998
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 95
    2. 21
    3. Pages: 12596-12601
  4. Type of Article: Article
  1. Abstract:

    To discover genes involved in von Hippel-Lindau (VHL)-mediated carcinogenesis, we used renal cell carcinoma cell lines stably transfected with wild-type VHL-expressing transgenes, Large-scale RNA differential display technology applied to these cell lines identified several differentially expressed genes, including an alpha carbonic anhydrase gene, termed CA12. The deduced protein sequence was classified as a one-pass transmembrane CA possessing an apparently intact catalytic domain in the extracellular CA module. Reintroduced wild-type VHL strongly inhibited the overexpression of the CA12 gene in the parental renal cell carcinoma cell lines. Similar results were obtained with CA9, encoding another transmembrane CA with an intact catalytic domain. Although both domains of the VHL protein contribute to regulation of CA12 expression, the elongin binding domain alone could effectively regulate CA9 expression. We mapped CA12 and CA9 loci to chromosome bands 15q22 and 17q21,2 respectively, regions prone to amplification in some human cancers. Additional experiments are needed to define the role of CA IX and CA XII enzymes in the regulation of pH in the extracellular microenvironment and its potential impact on cancer cell growth. [References: 40]

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