Abstract
We have compared the levels of phosphoglycerate mutase (EC 5.4.2.1), 2,3-bisphosphoglycerate phosphatase (EC 3.1.3.13), creatine kinase (EC 2.7.3.2) and enolase (EC 4.2.1.11) activities and the distribution of their isoenzymes in normal breast tissue and in breast carcinoma. Tumour tissue had higher phosphoglycerate mutase and enolase activity than normal tissue. Creatine kinase activity was higher in seven out of 12 tumours. In contrast 2,3-bisphosphoglycerate phosphatase activity was lower. Phosphoglycerate mutase, enolase and 2,3-bisphosphoglycerate phosphatase presented greater changes in the oestrogen receptor-negative/progesterone receptor-negative breast carcinomas than in the steroid receptor-positive tumours. Determined by electrophoresis, type BB phosphoglycerate mutase, type BB creatine kinase and αα-enolase were the major isoenzymes detected in normal breast tissue. Types αγ and γγ enolase, types MB and MM phosphoglycerate mutase were detected in much lower proportions. In tumours a decrease of phosphoglycerate mutase isoenzymes possessing M-type subunit and some increase of enolase isoenzymes possessing γ-type subunit was observed. No detectable change was observed in the creatine kinase phenotype. © 2000 Cancer Research Campaign
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References
Bais R and Edwards J (1982) Creatine kinase. Crit Rev Clin Lab Sci 16: 291–335
Bartrons R and Carreras J (1982) Purification and characterization of phosphoglycerate mutase isoenzymes from pig heart. Biochim Biophys Acta 708: 167–177
Bradford M (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254
Carreras J and Gallego C (1993) Metabolism of 2,3-bisphosphoglyceric acid in erythroid cells and tissues of vertebrates. Trends Comp Biochem Physiol 1: 421–450
Carreras J, Bartrons R, Climent F and Cussó R (1986) Bisphosphorylated metabolites of glycerate, glucose and fructose: functions, metabolism and molecular patholgy. Clin Biochem 19: 348–358
Chastain S, Ketchum C and Grizzle W (1988) Stability and electrophoretic characteristics of creatine kinase BB extracted from human brain and intestine. Clin Chem 334: 489–492
Crabtree B, Leech A and Newsholme A (1979) Measurement of enzyme activities in crude extracts of tissues. In: Techniques in the Live Sciences Vol B2/1, Kornberg HL, Metcalfe JC, Northcote DH, Pogson CI, Tipton KF (eds), B211/1–B211/37. Elservier/North Holland Biomedical Press: Amsterdam
Desjardins P (1982) Characterization of an atypical creatine kinase from human heart tissue, with properties similar to those of mitochondrial creatine kinase. Clin Chim Acta 121: 67–78
Durany N and Carreras J (1996) Distribution of phosphoglycerate mutase isozymes in rat, rabbit and human tissues. Comp Biochem Physiol 113: 217–223
Durany N, Joseph J, Campo E, Molina R and Carreras J (1997 a) Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas. Br J Cancer 76: 969–977
Durany N, Joseph J, Cruz-Sanchez F and Carreras J (1997 b) Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and creatine kinase activity and isoenzymes in human brain tumours. Br J Cancer 76: 1139–1149
Erikstein B, Nesland J, Ottestad L, Lund E and Johannessen J (1988) Neuron-specific enolase-positive breast carcinomas. Histol Histopathol 3: 97–102
Foreback C and Chu J (1981) Creatine kinase isoenzymes: electrophoretic and quantitative measurements. Crit Rev Clin Lab Sci 15: 187–230
Fothergill-Gilmore L and Watson H (1989) The phosphoglycerate mutases. Adv Enzymol 62: 227–313
Gerbitz K, Summer J and Schumacher I (1986) Enolase isoenzymes as tumour markers. J Clin Chem Clin Biochem 24: 1009–1016
Griffiths J (1982) Creatine kinase isoenzyme 1. Clin Lab Med 2: 493–506
Haimoto J, Takahashi Y, Koshikawa T, Nagura H and Kato K (1985) Immunohistochemical localization of γ-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest 52: 257–263
Hennipman A, Smits J, Van Oirschot B, Van Houwelingen J, Rijksen G, Neyt J, Van Unnik J and Staal G (1987) Glycolitic enzymes in breast cancer, benign breast disease and normal breast tissue. Tumor Biol 8: 251–263
Hennipman A, Van Oirschot B, Smits J, Rijksen G and Staal G (1988) Heterogeneity of glycolytic enzyme activity and isozyme composition of pyruvate kinase in breast cancer. Tumor Biol 9: 178–189
Ingelman-Sundberg H, Wikström B, Stormby N, Sundelin P and Hjerpe A (1989) Immunocytochemical reactivity of breast cancer tissue with antibodies to neuron-specific enolase and an adenocarcinoma-associated glycolipid antigen. Virchows Archiv A Pathol Anat 415: 539–544
Jares P, Rey M, Fernández P, Campo E, Nadal A, Muñoz M, Mallofré C, Muntané J, Nayach I, Estapé J and Cardesa A (1997) Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumor proliferation and estrogen receptor status. J Pathol 182: 160–166
Joseph J, Cardesa A and Carreras J (1997) Creatine kinase activity and isoenzymes in lung, colon and liver carcinomas. Br J Cancer 76: 100–105
Joseph J, Cruz-Sánchez F and Carreras J (1996) Enolase activity and isoenzyme distribution in human brain regions and tumors. J Neurochem 66: 2484–2490
Kaiser E, Kuzmits R, Pregant P, Burghuber O and Worofka W (1989) Clinical biochemistry of neuron specific enolase. Clin Chim Acta 183: 13–32
Kanemitsu F and Okigaki T (1988) Creatine kinase: a review. J Cromatog 429: 399–417
Kato K, Ishiguro Y and Ariyoshi Y (1983) Enolase isozymes as disease markers: distribution of three enolase subunits (α, β and γ) in various human tissues. Disease Markers 1: 213–220
Kaye A (1983) Enzyme induction by strogen. J Steroid Biochem 19: 33–40
Kaye A, Reiss N, Shaer A, Sluyser M, Iacobelli S, Amroch D and Soffer Y (1981) Estrogen responsive creatine kinase in normal and neoplastic cells. J Steroid Biochem 15: 69–75
Kaye A, Hallowes R, Cox S and Sluyser M (1986) Hormone-responsive creatine kinase in normal and neoplastic mammary glands. Ann NY Acad Sci 464: 218–230
Klein B and Jeunelot C (1978) Anion-exchange chromatography of erythrocytic and muscle adenylate kinase and its effect on the serum creatine kinase isoenzyme assays. Clin Chem 24: 2168–2170
Klinga K, Kaufman M, Runnebaum B and Kubli F (1982) Distribution of estrogen and progesterone receptors in primary tumor and lymphnodes in individual patients with breast cancer. Oncology 39: 337–339
Lakatua D and Mohammed R (1986) Estrogen and progesterone receptors and creatine kinase isoenzymes in human breast cancer. Clin Chem 32: 2103–2104
Lilleng R, Hagmar B and Nesland J (1992) C- erb B-2 protein and neuroendocrine expression in intraductal carcinomas of the breast. Mod Pathol 5: 41–47
Lindsey G and Diamond E (1978) Evidence for significant quantities of creatine kinase MM isoenzyme in human brain. Biochim Biophys Acta 524: 78–84
McCarty K Jr, Miller L, Cox E, Konrath J and McCarty K (1985) Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med 109: 716–722
Marangos P and Schmechel D (1987) Neuron specific enolase, a clinically useful marker for neurons and nonendocrine cells. Annu Rev Neurosci 10: 269–295
Matsushima S, Mori M, Adachi Y, Matsukuma A and Sugimachi K (1994) S100 protein positive human breast carcinomas: an immunohistochemical study. J Surg Oncol 55: 108–113
Messeri G, Tozzi P, Boddi V and Ciatto S (1983) Glucose-6-phosphate dehydrogenase activity and estrogen receptors in human breast cancer. J Steroid Biochem 19: 1647–1650
Meyer I, Thompson J, Kiser E and Haven G (1980) Observation of a variant creatine kinase isoenzyme in sera and breast tumor cytosols. Am J Clin Pathol 74: 332–336
Nanji A (1983) Serum creatine kinase isoenzymes: a review. Muscle Nerve 6: 83–90
Nesland J, Memoli V, Holm R, Gould V and Johannessen J (1985) Breast carcinomas with neuroendocrine differentiation. Ultrastruct Pathol 8: 225–240
Nesland J, Holm R and Johannessen J (1986 a) A study of different markers for neuroendocrine differentiation in breast carcinomas. Path Res Pract 181: 524–530
Nesland J, Holm R, Johannessen J and Gould V (1986 b) Neurone-specific enolase immunostaining in the diagnosis of breast carcinomas with neuroendocrine differentiation. Its usefulness and limitations. J Pathol 148: 35–43
Nesland J, Lundi S, Holm R and Johannessen J (1987) Electron microscopy and immunostaining of the normal breast and its benign lesions: a search for neuroendocrine cells. Histol Histopath 2: 73–77
Nesland J, Holm R, Johannessen J and Gould V (1988) Neuroendocrine differentiation in breast lesions. Path Res Pract 183: 214–221
Nesland J, Ottestad L, Heikilla R, Holm R, Tveit K and Borresen A-L (1991 a) C- erb B-2 protein and neuroendocrine expression in breast carcinomas. Anticancer Res 11: 161–168
Nesland J, Ottestad L, Borresen A-L, Tvedt K, Holm R, Heikkilä R and Tveit K (1991 b) The c- erb B-2 protein in primary and metastatic breast carcinomas. Ultrastruct Pathol 15: 281–289
Omenn G and Cheung C-Y (1974) Phosphoglycerate mutase isozyme marker for tissue differentiation in man. Am J Hum Genet 26: 393–399
Omenn G and Hermodson M (1975) Human phosphoglycerate mutase: isozyme marker for muscle differentiation and for neoplasia. In Isozymes Vol. 3, (Markert Cl ed) pp. 1005–1019. Academic Press: New York
Osborne K (1985) Heterogeneity in hormone receptor status in primary and metastatic breast cancer. Semin Oncol 12: 317–326
Pahlman S, Esscher T and Nilsson K (1986) Expression of γ-subunit of enolase, neuron-specific enolase, in human non-neuroendocrine tumors and derived cell lines. Lab Invest 54: 554–560
Pertschuk L, Eisenberg K and Carter A (1985) Heterogeneity of estrogen binding sites in breast cancer: morphologic demonstration and relationship to endocrine response. Breast Cancer Res Treat 5: 137–147
Rapoport S (1968) The regulation of glycolysis in mammalian erythrocytes. Essays Biochem 4: 69–103
Reeve J, Stewart J, Watson D, Wulfrank D, Twentyman P and Bleehen N (1986) Neuron specific enolase expression in carcinoma of the lung. Br J Cancer 53: 519–528
Royds J, Taylor C and Timperley W (1985) Enolase isoenzymes as diagnostic markers. Neophatol Appl Neurobiol 11: 1–16
Scambia G, Natoli V, Panici P, Sica G and Mancuso S (1986 a). J Cancer Res Clin Oncol 112: 29–32
Scambia G, Panici P, Sica G, Natoli V, Caruso A and Mancuso S (1986 b) Creatine kinase activity and steroidal hormone receptors in primary breast cancer. Ann N Y Acad Sci 464: 511–513
Scambia G, Santeunasio G, Panici P, Iacobelli S and Mancuso S (1988) Immunochemical localization of creatine kinase BB in primary breast cancer: correlation with estrogen receptor content. J Cancer Res Clin Oncol 114: 101–104
Schmechel D (1985) γ-Subunit of the glycolitic enzyme enolase: nonspecific or neuron specific?. Lab Invest 52: 239–242
Schmechel D, Marangos P and Brightman M (1978) Neuron-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature 276: 834–836
Scopsi L, Andreola S, Pilotti S, Testori A, Baldini M, Leoni F, Lombardi L, Hutton J, Shimizu F and Rosa P (1992) Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters. Am J Surg Pathol 16: 561–576
Taylor C, Royds J, Parsons M and Timperley W (1983) Diagnostic aspects of enolase isozymes. Curr Topics Biol Med Res 11: 95–119
Tsung A (1983) Creatine kinase activity and isoenzyme pattern in various normal tissues and neoplasms. Clin Chem 29: 2040–2043
Urdal P, Urdal K and Stromme J (1983) Cytoplasmic creatine kinase isoenzymes quantitated in tissue specimens obtained at surgery. Clin Chem 29: 310–313
Vinores S, Bonnin J, Rubinstein L and Marangos P (1984) Immunohistochemical demonstration of neuron-specific enolase in neoplasms of the CNS and other tissues. Arch Pathol Lab Med 108: 536–539
Wallimann T, Wyss M, Bridiczka D, Nicolay K and Eppenberger M (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostais. Biochem J 281: 21–40
Wilander E, Phalman S, Sällström J and Lindgrem A (1987) Neuron-specific enolase expression and neuroendocrine differentiation in carcinomas of the breast. Arch Pathol Lab Med 111: 830–832
Winstend S and Hopps J (1985) Enzyme studies in breast tumor cytosols. Clin Chem 31: 986
Wold F (1971) Enolase. In: The Enzymes Vol V, Boyer PD (ed), pp. 499–538. Academic Press: New York
Wold L, Chin-Yang L and Homburger H (1981) Localization of the B and M polypeptide subunits of creatine kinase in normal and neoplastic human tissues by an immunoperoxidase technic. Am J Clin Pathol 75: 327–332
Wyss M, Smeitink J, Wevers R and Wallimann T (1992) Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism. Biochim Biophys Acta 1102: 119–166
Zarghami N, Yu H, Diamandis E and Sutherland D (1995) Quantification of creatine kinase BB isoenzyme in tumor cytosols and serum with an ultrasensitive time-resolved immunofluorometric technique. Clin Biochem 28: 243–253
Zarghami N, Giai M, Yu H, Roagna R, Ponzone R, Katsaros D, Sismondi P and Diamandis E (1996) Ceratine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients. Br J Cancer 73: 386–390
Zeltzer P, Schneider S, Marangos P and Zweig M (1986) Differential expression of neural isozymes by human medulloblastomas and gliomas and neuroectodermal cell lines. J Natl Cancer Inst 77: 625–631
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Durany, N., Joseph, J., Jimenez, O. et al. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma. Br J Cancer 82, 20–27 (2000). https://doi.org/10.1054/bjoc.1999.0871
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DOI: https://doi.org/10.1054/bjoc.1999.0871
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