HumanMN/CA9Gene, a Novel Member of the Carbonic Anhydrase Family: Structure and Exon to Protein Domain Relationships

Opavský, René; Pastoreková, Silvia; Zelnik, V.; Gibadulinová, Adriana; Stanbridge, Eric J.; Závada, Jan; Kettmann, Richard; Pastorek, Jaromı́r

doi:10.1006/geno.1996.0223

Cited by 342 publications

(303 citation statements)

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“…It answers all the questions listed in the introductory paragraph: s-CA IX is being shed from the cells into the culture medium, and compared with cell-associated protein p54/58, it is somewhat shortened (to 50 and 54 kDa). This size corresponds to the extracellular part of the CA IX molecule, which is composed of proteoglycan (PG)-like and CA domains that have been cleaved off the rest of the molecule -the transmembrane (TM) segment and intracellular (IC) tail of CA IX (Opavský et al, 1996). The s-CA IX contains both PG and CA domains, since it reacts with both mAb M75 specific for PG and with MAb V-10 specific for the CA domain.…”

Section: Discussionmentioning

confidence: 99%

Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

et al. 2003

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Tumour-associated protein carbonic anhydrase IX (CA IX) has two major forms. One is a cell-associated, transmembrane protein seen on Western blots as a twin band of 54/58 kDa, expressed in gastric mucosa and in several types of cancer. The other is a soluble protein s-CA IX of 50/54 kDa, which is released into the culture medium or into the body fluids, most likely by proteolytic cleavage of the extracellular part from transmembrane and intracellular sequences. While TC media of CA IX-positive tumour cell lines or shortterm cultures of tumour explants contain a relatively high concentration of s-CA IX (20 -50 ng ml À1 ), the level of this antigen in blood serum and urine of renal clear cell carcinoma patients is about 1000 Â lower. The concentration of CA IX in the blood and in urine varies within wide limits and there is no obvious correlation with tumour size. After nephrectomy, s-CA IX is cleared from the blood within a few days. Only an extremely low concentration of CA IX was detectable in the sera and in urine of control individuals.

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Section: Discussionmentioning

confidence: 99%

Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

et al. 2003

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“…According to the results, this was followed by a series of 6-12 aa oligopeptides. A major part of the PG domain consists of a sixfold tandem repeat of six aa (aa 61-96); four repeats are identical (GEEDLP) and two contain two aa exchanged (SEEDSP and REEDPP) (Opavsky et al, 1996). Figure 3 shows the result of competition ELISA with recombinant MN/CA IX and oligopetides synthesized according to partial sequences of the PG region.…”

Section: Identification Of the Epitope Recognized By Mab M75mentioning

confidence: 99%

Human tumour-associated cell adhesion protein MN/CA IX: identification of M75 epitope and of the region mediating cell adhesion

et al. 2000

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MN/CA IX is a cell surface protein, strongly associated with several types of human carcinomas. It exerts activity of carbonic anhydrase and capacity of binding to cell surface receptors. In the present work, we used affinity purified MN/CA IX protein to demonstrate that the cells adhere to immobilized MN/CA IX and that the monoclonal antibody M75 abrogates cell attachment to MN/CA IX. Using synthetic oligopeptides, we identified M75 epitope and located it in the proteoglycan domain, which contains a sixfold tandem repeat of six amino acids GEEDLP. From phage display library of random heptapeptides we identified and chemically synthesized those which compete for the epitope with M75 and inhibit adhesion of cells to MN/CA IX. These heptapeptides might serve as lead compounds for drug design. © 2000 Cancer Research Campaign

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“…The fate of the pyruvate molecules produced depends on the oxygen presence. Adequate oxygenation allows the conversion of pyruvate to ATP, water and carbon dioxide, the reversible transformation of which to carbonic acid is catalysed by the enzyme carbonic anhydrase (Opavsky et al, 1996). Lack of oxygen or biochemical defects relevant to the electron transport system or the citric acid cycle restricts ATP production to glycolysis.…”

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Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis

et al. 2003

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Lactate dehydrogenase-5 (LDH-5) catalyses the reversible transformation of pyruvate to lactate, having a principal position in the anaerobic cellular metabolism. Induction of LDH-5 occurs during hypoxia and LDH-5 transcription is directly regulated by the hypoxia-inducible factor 1 (HIF1). Serum LDH levels have been correlated with poor prognosis and resistance to chemotherapy and radiotherapy in various neoplastic diseases. The expression, however, of LDH in tumours has never been investigated in the past. In the present study, we established an immunohistochemical method to evaluate the LDH-5 overexpression in tumours, using two novel antibodies raised against the rat muscle LDH-5 and the human LDH-5 (Abcam, UK). The subcellular patterns of expression in cancer cells were mixed nuclear and cytoplasmic. In direct contrast to cancer cells, stromal fibroblasts were reactive for LDH-5 only in a minority of cases. Serum LDH, although positively correlated with, does not reliably reflect the intratumoral LDH-5 status. Lactate dehydrogenase-5 overexpression was directly related to HIF1a and 2a, but not with the carbonic anhydrase 9 expression. Patients with tumours bearing high LDH-5 expression had a poor prognosis. Tumours with simultaneous LDH-5 and HIF1a (or HIF2a) overexpression, indicative of a functional HIF pathway, had a particularly aggressive behaviour. It is concluded that overexpression of LDH-5 is a common event in non-small-cell lung cancer, can be easily assessed in paraffin-embedded material and provides important prognostic information, particularly when combined with other endogenous markers of hypoxia and acidity.

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HumanMN/CA9Gene, a Novel Member of the Carbonic Anhydrase Family: Structure and Exon to Protein Domain Relationships

Cited by 342 publications

References 0 publications

Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

Soluble form of carbonic anhydrase IX (CA IX) in the serum and urine of renal carcinoma patients

Human tumour-associated cell adhesion protein MN/CA IX: identification of M75 epitope and of the region mediating cell adhesion

Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis

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