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
Keywords: 2,3-bisphosphoglycerate phosphatase; creatine kinase; enolase; phosphoglycerate mutase activity and isoenzymes; breast carcinoma
Full Text
The Full Text of this article is available as a PDF (123.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Avril M. F., Auperin A., Margulis A., Gerbaulet A., Duvillard P., Benhamou E., Guillaume J. C., Chalon R., Petit J. Y., Sancho-Garnier H. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study. Br J Cancer. 1997;76(1):100–106. doi: 10.1038/bjc.1997.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bais R., Edwards J. B. Creatine kinase. Crit Rev Clin Lab Sci. 1982;16(4):291–335. doi: 10.3109/10408368209107030. [DOI] [PubMed] [Google Scholar]
- Bartrons R., Carreras J. Purification and characterization of phosphoglycerate mutase isozymes from pig heart. Biochim Biophys Acta. 1982 Nov 9;708(2):167–177. doi: 10.1016/0167-4838(82)90217-5. [DOI] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
- Carreras J., Bartrons R., Climent F., Cusso R. Bisphosphorylated metabolites of glycerate, glucose, and fructose: functions, metabolism and molecular pathology. Clin Biochem. 1986 Dec;19(6):348–358. doi: 10.1016/s0009-9120(86)80008-x. [DOI] [PubMed] [Google Scholar]
- Chastain S. L., Ketchum C. H., Grizzle W. E. Stability and electrophoretic characteristics of creatine kinase BB extracted from human brain and intestine. Clin Chem. 1988 Mar;34(3):489–492. [PubMed] [Google Scholar]
- Desjardins P. R. Characterization of an atypical creatine kinase from human heart tissue, with properties similar to those of mitochondrial creatine kinase. Clin Chim Acta. 1982 May 6;121(1):67–78. doi: 10.1016/0009-8981(82)90212-1. [DOI] [PubMed] [Google Scholar]
- Durany N., Carreras J. Distribution of phosphoglycerate mutase isozymes in rat, rabbit and human tissues. Comp Biochem Physiol B Biochem Mol Biol. 1996 Jun;114(2):217–223. doi: 10.1016/0305-0491(95)02135-3. [DOI] [PubMed] [Google Scholar]
- Durany N., Joseph J., Campo E., Molina R., Carreras J. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and enolase activity and isoenzymes in lung, colon and liver carcinomas. Br J Cancer. 1997;75(7):969–977. doi: 10.1038/bjc.1997.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Durany N., Joseph J., Cruz-Sánchez F. F., Carreras J. Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase and creatine kinase activity and isoenzymes in human brain tumours. Br J Cancer. 1997;76(9):1139–1149. doi: 10.1038/bjc.1997.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erikstein B., Nesland J. M., Ottestad L., Lund E., Johannessen J. V. Neuron specific enolase-positive breast carcinomas. Histol Histopathol. 1988 Jan;3(1):97–102. [PubMed] [Google Scholar]
- Foreback C. C., Chu J. W. Creatine kinase isoenzymes: electrophoretic and quantitative measurements. Crit Rev Clin Lab Sci. 1981;15(3):187–230. doi: 10.3109/10408368109105871. [DOI] [PubMed] [Google Scholar]
- Fothergill-Gilmore L. A., Watson H. C. The phosphoglycerate mutases. Adv Enzymol Relat Areas Mol Biol. 1989;62:227–313. doi: 10.1002/9780470123089.ch6. [DOI] [PubMed] [Google Scholar]
- Gerbitz K. D., Summer J., Schumacher I., Arnold H., Kraft A., Mross K. Enolase isoenzymes as tumour markers. J Clin Chem Clin Biochem. 1986 Dec;24(12):1009–1016. doi: 10.1515/cclm.1986.24.12.1009. [DOI] [PubMed] [Google Scholar]
- Griffiths J. C. Creatine kinase isoenzyme 1. Clin Lab Med. 1982 Sep;2(3):493–506. [PubMed] [Google Scholar]
- Haimoto H., Takahashi Y., Koshikawa T., Nagura H., Kato K. Immunohistochemical localization of gamma-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest. 1985 Mar;52(3):257–263. [PubMed] [Google Scholar]
- Hennipman A., Smits J., van Oirschot B., van Houwelingen J. C., Rijksen G., Neyt J. P., Van Unnik J. A., Staal G. E. Glycolytic enzymes in breast cancer, benign breast disease and normal breast tissue. Tumour Biol. 1987;8(5):251–263. doi: 10.1159/000217529. [DOI] [PubMed] [Google Scholar]
- Hennipman A., van Oirschot B. A., Smits J., Rijksen G., Staal G. E. Heterogeneity of glycolytic enzyme activity and isozyme composition of pyruvate kinase in breast cancer. Tumour Biol. 1988;9(4):178–189. doi: 10.1159/000217560. [DOI] [PubMed] [Google Scholar]
- Ingelman-Sundberg H., Wikström B., Stormy N., Sundelin P., Hjerpe A. Immunocytochemical reactivity of breast cancer tissue with antibodies to neuron-specific enolase and an adenocarcinoma-associated glycolipid antigen. Virchows Arch A Pathol Anat Histopathol. 1989;415(6):539–544. doi: 10.1007/BF00718647. [DOI] [PubMed] [Google Scholar]
- Jares P., Rey M. J., Fernández P. L., Campo E., Nadal A., Muñoz M., Mallofré C., Muntané J., Nayach I., Estapé J. Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status. J Pathol. 1997 Jun;182(2):160–166. doi: 10.1002/(SICI)1096-9896(199706)182:2<160::AID-PATH814>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
- Joseph J., Cruz-Sánchez F. F., Carreras J. Enolase activity and isoenzyme distribution in human brain regions and tumors. J Neurochem. 1996 Jun;66(6):2484–2490. doi: 10.1046/j.1471-4159.1996.66062484.x. [DOI] [PubMed] [Google Scholar]
- Kaiser E., Kuzmits R., Pregant P., Burghuber O., Worofka W. Clinical biochemistry of neuron specific enolase. Clin Chim Acta. 1989 Jul 31;183(1):13–31. doi: 10.1016/0009-8981(89)90268-4. [DOI] [PubMed] [Google Scholar]
- Kanemitsu F., Okigaki T. Creatine kinase isoenzymes. J Chromatogr. 1988 Jul 29;429:399–417. doi: 10.1016/s0378-4347(00)83880-3. [DOI] [PubMed] [Google Scholar]
- Kaye A. M. Enzyme induction by estrogen. J Steroid Biochem. 1983 Jul;19(1A):33–40. [PubMed] [Google Scholar]
- Kaye A. M., Hallowes R., Cox S., Sluyser M. Hormone-responsive creatine kinase in normal and neoplastic mammary glands. Ann N Y Acad Sci. 1986;464:218–230. doi: 10.1111/j.1749-6632.1986.tb16006.x. [DOI] [PubMed] [Google Scholar]
- Kaye A. M., Reiss N., Shaer A., Sluyser M., Iacobelli S., Amroch D., Soffer Y. Estrogen responsive creatine kinase in normal and neoplastic cells. J Steroid Biochem. 1981 Dec;15:69–75. doi: 10.1016/0022-4731(81)90260-0. [DOI] [PubMed] [Google Scholar]
- Klein B., Jeunelot C. L. Anion-exchange chromatography of erythrocytic and muscle adenylate kinase and its effect on the serum creatine kinase isoenzyme assays. Clin Chem. 1978 Dec;24(12):2168–2170. [PubMed] [Google Scholar]
- Klinga K., Kaufmann M., Runnebaum B., Kubli F. Distribution of estrogen and progesterone receptors on primary tumor and lymph nodes in individual patients with breast cancer. Oncology. 1982;39(6):337–339. doi: 10.1159/000225666. [DOI] [PubMed] [Google Scholar]
- Lakatua D. J., Mohammed R. Estrogen and progesterone receptors and creatine kinase isoenzymes in human breast cancer. Clin Chem. 1986 Nov;32(11):2103–2104. [PubMed] [Google Scholar]
- Lilleng R., Hagmar B. M., Nesland J. M. C-erbB-2 protein and neuroendocrine expression in intraductal carcinomas of the breast. Mod Pathol. 1992 Jan;5(1):41–47. [PubMed] [Google Scholar]
- Lindsey G. G., Diamond E. M. Evidence for significant quantities of creatine kinase MM isoenzyme in human brain. Biochim Biophys Acta. 1978 May 11;524(1):78–84. doi: 10.1016/0005-2744(78)90105-5. [DOI] [PubMed] [Google Scholar]
- Marangos P. J., Schmechel D. E. Neuron specific enolase, a clinically useful marker for neurons and neuroendocrine cells. Annu Rev Neurosci. 1987;10:269–295. doi: 10.1146/annurev.ne.10.030187.001413. [DOI] [PubMed] [Google Scholar]
- Matsushima S., Mori M., Adachi Y., Matsukuma A., Sugimachi K. S100 protein positive human breast carcinomas: an immunohistochemical study. J Surg Oncol. 1994 Feb;55(2):108–113. doi: 10.1002/jso.2930550210. [DOI] [PubMed] [Google Scholar]
- McCarty K. S., Jr, Miller L. S., Cox E. B., Konrath J., McCarty K. S., Sr Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med. 1985 Aug;109(8):716–721. [PubMed] [Google Scholar]
- Messeri G., Tozzi P., Boddi V., Ciatto S. Glucose-6-phosphate dehydrogenase activity and estrogen receptors in human breast cancer. J Steroid Biochem. 1983 Nov;19(5):1647–1650. doi: 10.1016/0022-4731(83)90384-9. [DOI] [PubMed] [Google Scholar]
- Meyer I. J., Thompson J. A., Kiser E. J., Haven G. T. Observation of a variant creatine kinase isoenzyme in sera and breast tumor cytosols. Am J Clin Pathol. 1980 Sep;74(3):332–336. doi: 10.1093/ajcp/74.3.332. [DOI] [PubMed] [Google Scholar]
- Nanji A. A. Serum creatine kinase isoenzymes: a review. Muscle Nerve. 1983 Feb;6(2):83–90. doi: 10.1002/mus.880060203. [DOI] [PubMed] [Google Scholar]
- Nesland J. M., Holm R., Johannessen J. V. A study of different markers for neuroendocrine differentiation in breast carcinomas. Pathol Res Pract. 1986 Oct;181(5):524–530. doi: 10.1016/S0344-0338(86)80144-3. [DOI] [PubMed] [Google Scholar]
- Nesland J. M., Holm R., Johannessen J. V., Gould V. E. Neuroendocrine differentiation in breast lesions. Pathol Res Pract. 1988 Apr;183(2):214–221. doi: 10.1016/S0344-0338(88)80048-7. [DOI] [PubMed] [Google Scholar]
- Nesland J. M., Holm R., Johannessen J. V., Gould V. E. Neurone specific enolase immunostaining in the diagnosis of breast carcinomas with neuroendocrine differentiation. Its usefulness and limitations. J Pathol. 1986 Jan;148(1):35–43. doi: 10.1002/path.1711480107. [DOI] [PubMed] [Google Scholar]
- Nesland J. M., Lunde S., Holm R., Johannessen J. V. Electron microscopy and immunostaining of the normal breast and its benign lesions. A search for neuroendocrine cells. Histol Histopathol. 1987 Jan;2(1):73–77. [PubMed] [Google Scholar]
- Nesland J. M., Memoli V. A., Holm R., Gould V. E., Johannessen J. V. Breast carcinomas with neuroendocrine differentiation. Ultrastruct Pathol. 1985;8(2-3):225–240. doi: 10.3109/01913128509142155. [DOI] [PubMed] [Google Scholar]
- Nesland J. M., Ottestad L., Børresen A. L., Tvedt K. E., Holm R., Heikkilä R., Tveit K. The c-erbB-2 protein in primary and metastatic breast carcinomas. Ultrastruct Pathol. 1991 May-Jun;15(3):281–289. doi: 10.3109/01913129109021890. [DOI] [PubMed] [Google Scholar]
- Nesland J. M., Ottestad L., Heikilla R., Holm R., Tveit K., Børresen A. L. C-erbB-2 protein and neuroendocrine expression in breast carcinomas. Anticancer Res. 1991 Jan-Feb;11(1):161–167. [PubMed] [Google Scholar]
- Omenn G. S., Cheung S. C. Phosphoglycerate mutase isozyme marker for tissue differentiation in man. Am J Hum Genet. 1974 May;26(3):393–399. [PMC free article] [PubMed] [Google Scholar]
- Osborne C. K. Heterogeneity in hormone receptor status in primary and metastatic breast cancer. Semin Oncol. 1985 Sep;12(3):317–326. [PubMed] [Google Scholar]
- Pertschuk L. P., Eisenberg K. B., Carter A. C., Feldman J. G. Heterogeneity of estrogen binding sites in breast cancer: morphologic demonstration and relationship to endocrine response. Breast Cancer Res Treat. 1985;5(2):137–147. doi: 10.1007/BF01805987. [DOI] [PubMed] [Google Scholar]
- Påhlman S., Esscher T., Nilsson K. Expression of gamma-subunit of enolase, neuron-specific enolase, in human non-neuroendocrine tumors and derived cell lines. Lab Invest. 1986 May;54(5):554–560. [PubMed] [Google Scholar]
- Rapoport S. The regulation of glycolysis in mammalian erythrocytes. Essays Biochem. 1968;4:69–103. [PubMed] [Google Scholar]
- Reeve J. G., Stewart J., Watson J. V., Wulfrank D., Twentyman P. R., Bleehen N. M. Neuron specific enolase expression in carcinoma of the lung. Br J Cancer. 1986 Apr;53(4):519–528. doi: 10.1038/bjc.1986.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Royds J. A., Taylor C. B., Timperley W. R. Enolase isoenzymes as diagnostic markers. Neuropathol Appl Neurobiol. 1985 Jan-Feb;11(1):1–16. doi: 10.1111/j.1365-2990.1985.tb00001.x. [DOI] [PubMed] [Google Scholar]
- Scambia G., Natoli V., Panici P. B., Sica G., Mancuso S. Estrogen responsive creatine kinase in human breast cancer cells. J Cancer Res Clin Oncol. 1986;112(1):29–32. doi: 10.1007/BF00394935. [DOI] [PubMed] [Google Scholar]
- Scambia G., Santeusanio G., Panici P. B., Iacobelli S., Mancuso S. Immunohistochemical localization of creatine kinase BB in primary breast cancer: correlation with estrogen receptor content. J Cancer Res Clin Oncol. 1988;114(1):101–104. doi: 10.1007/BF00390493. [DOI] [PubMed] [Google Scholar]
- Schmechel D. E. Gamma-subunit of the glycolytic enzyme enolase: nonspecific or neuron specific? Lab Invest. 1985 Mar;52(3):239–242. [PubMed] [Google Scholar]
- Schmechel D., Marangos P. J., Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. 1978 Dec 21;276(5690):834–836. doi: 10.1038/276834a0. [DOI] [PubMed] [Google Scholar]
- Scopsi L., Andreola S., Pilotti S., Testori A., Baldini M. T., Leoni F., Lombardi L., Hutton J. C., Shimizu F., Rosa P. Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters. Am J Surg Pathol. 1992 Jun;16(6):561–576. doi: 10.1097/00000478-199206000-00004. [DOI] [PubMed] [Google Scholar]
- Taylor C. B., Royds J. A., Parsons M. A., Timperley W. R. Diagnostic aspects of enolase isozymes. Isozymes Curr Top Biol Med Res. 1983;11:95–119. [PubMed] [Google Scholar]
- Tsung S. H. Creatine kinase activity and isoenzyme pattern in various normal tissues and neoplasms. Clin Chem. 1983 Dec;29(12):2040–2043. [PubMed] [Google Scholar]
- Urdal P., Urdal K., Strømme J. H. Cytoplasmic creatine kinase isoenzymes quantitated in tissue specimens obtained at surgery. Clin Chem. 1983 Feb;29(2):310–313. [PubMed] [Google Scholar]
- Vinores S. A., Bonnin J. M., Rubinstein L. J., Marangos P. J. Immunohistochemical demonstration of neuron-specific enolase in neoplasms of the CNS and other tissues. Arch Pathol Lab Med. 1984 Jul;108(7):536–540. [PubMed] [Google Scholar]
- Wallimann T., Wyss M., Brdiczka D., Nicolay K., Eppenberger H. M. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281(Pt 1):21–40. doi: 10.1042/bj2810021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilander E., Påhlman S., Sällström J., Lindgren A. Neuron-specific enolase expression and neuroendocrine differentiation in carcinomas of the breast. Arch Pathol Lab Med. 1987 Sep;111(9):830–832. [PubMed] [Google Scholar]
- Wold L. E., Li C. Y., Homburger H. A. 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. 1981 Mar;75(3):327–332. doi: 10.1093/ajcp/75.3.327. [DOI] [PubMed] [Google Scholar]
- Wyss M., Smeitink J., Wevers R. A., Wallimann T. Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism. Biochim Biophys Acta. 1992 Sep 25;1102(2):119–166. doi: 10.1016/0005-2728(92)90096-k. [DOI] [PubMed] [Google Scholar]
- Zarghami N., Giai M., Yu H., Roagna R., Ponzone R., Katsaros D., Sismondi P., Diamandis E. P. Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients. Br J Cancer. 1996 Feb;73(3):386–390. doi: 10.1038/bjc.1996.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zarghami N., Yu H., Diamandis E. P., Sutherland D. J. Quantification of creatine kinase BB isoenzyme in tumor cytosols and serum with an ultrasensitive time-resolved immunofluorometric technique. Clin Biochem. 1995 Jun;28(3):243–253. doi: 10.1016/0009-9120(95)00010-7. [DOI] [PubMed] [Google Scholar]
- Zeltzer P. M., Schneider S. L., Marangos P. J., Zweig M. H. Differential expression of neural isozymes by human medulloblastomas and gliomas and neuroectodermal cell lines. J Natl Cancer Inst. 1986 Sep;77(3):625–631. doi: 10.1093/jnci/77.3.625. [DOI] [PubMed] [Google Scholar]