Arsenic, cadmium and neuron specific enolase (ENO2, γ-enolase) expression in breast cancer

Cancer Cell International

Donald A Sens¹  Christina Allen¹  Chandra S Bathula¹  Mary Ann Sens¹  Xu Dong Zhou¹  Jane R Dunlevy²  Seema Somji¹  Scott H Garrett¹  Maureen A Soh¹ 

[1] Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA;Department of Anatomy and Cell Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND, USA

关键词: ENO2;    neuron specific enolase;    ENO;    enolase;    MCF-10A;    breast epithelial cells;    breast cancer;    cadmium;    arsenic;    Biomarker;   

Others  :  795340
DOI  :  10.1186/1475-2867-11-41

 received in 2011-08-17, accepted in 2011-11-18,  发布年份 2011

【 摘 要 】

Background

Neuron specific enolase (ENO2, γ-enolase) has been used as a biomarker to help identify neuroendocrine differentiation in breast cancer. The goal of the present study was to determine if ENO2 expression in the breast epithelial cell is influenced by the environmental pollutants, arsenite and cadmium. Acute and chronic exposure of MCF-10A cells to As⁺³ and Cd⁺² sufficient to allow colony formation in soft agar, was used to determine if ENO2 expression was altered by these pollutants.

Results

It was shown that both As⁺³ and Cd⁺² exposure caused significant increases in ENO2 expression under conditions of both acute and chronic exposure. In contrast, ENO1, the major glycolytic enolase in non-muscle and neuronal cells, was largely unaffected by exposure to either As⁺³ or Cd⁺². Localization studies showed that ENO2 in the MCF-10A cells transformed by As⁺³ or Cd⁺² had both a cytoplasmic and nuclear localization. In contrast, ENO1 was localized to the cytoplasm. ENO2 localized to the cytoplasm was found to co-localized with ENO1.

Conclusion

The results are the first to show that ENO2 expression in breast epithelial cells is induced by acute and chronic exposure to As⁺³ or Cd⁺². The findings also suggest a possible link between As⁺³ and Cd⁺² exposure and neuroendocrine differentiation in tumors. Overall, the results suggest that ENO2 might be developed as a biomarker indicating acute and/or chronic environmental exposure of the breast epithelial cell to As⁺³ and Cd⁺².

【 授权许可】

   
2011 Soh et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Ellis IO: Immunocytochemistry in diagnostic pathology. In Theory and practice of histological techniques. Edited by Bancroft JD, Stevens A. Edinburgh: Churchill Livingstone; 1995:471.
• [2]Wold F: Enolase. In The Enzymes. Volume 5. Edited by Boyer PD. Academic Press: New York; 1971::499-538.
• [3]Schmechel D, Marangos P, Brightman M: Neuron-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature 1978, 276:834-836.
• [4]Kato K, Ishiguro Y, Ariyoshi Y: Enolase isoenzymes as disease markers: distribution of three enolase subunits (α, β and γ) in various human tissues. Disease Markers 1983, 1:213-220.
• [5]Haimoto J, Takahashi Y, Koshikawa T, Nagura H, Kato K: Immunohistochemical localization of γ-enolase in normal human tissues other than nervous and neuroendocrine tissues. Lab Invest 1985, 52:257-263.
• [6]Durany N, Joseph J, Jimenez OM, Climent F, Fernandez PL, Rivera F, Carreras J: Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinomas. Br J Cancer 2000, 82:20-27.
• [7]Vinores S, Bonnin J, Rubinstein L, Marangos P: Immunohistochemical demonstration of neuron-specific enolase in neoplasms of the CNS and other tissues. Arch Pathol Lab Med 1984, 108:536-539.
• [8]Nesland J, Holm R, Johannessen J, Gould V: Neuron-specific enolase immunostaining in the diagnosis of breast carcinomas with neuroendocrine differentiation. Its usefulness and limitations. J Pathol 1986, 148:35-43.
• [9]Nesland J, Lundi S, Holm R, Johannessen J: Electron microscopy and immunostaining of the normal breast and its benign lesions: a search for neuroendocrine cells. Histol. Histopathol 1987, 2:73-77.
• [10]Nesland J, Holm R, Johannessen J, Gould V: Neuroendocrine differentiation in breast lesions. Path Res Pract 1988, 183:214-221.
• [11]Nesland J, Holm R, Johannessen J: A study of different markers for neuroendocrine differentiation in breast carcinomas. Path Res Pract 1986, 181:524-530.
• [12]Nesland J, Ottestad L, Heikilla R, Holm R, Tveit K, Borresen AL: C-erbB-2 protein and neuroendocrine expression in breast carcinomas. Anticancer Res 1991, 11:161-168.
• [13]Nesland J, Ottestad L, Borresen AL, Tvedt K, Holm R, Heikkila R, Tveit K: The c-erbB2 protein in primary and metastatic breast carcinomas. Ultrastruct Pathol 1991, 15:281-289.
• [14]Wilander E, Phalman S, Sallstrom J, Lindgrem A: Neuron-specific enolase expression and neuroendocrine differentiation in carcinomas of the breast. Arch Pathol Lab Med 1987, 111:830-832.
• [15]Erikstein B, Nesland J, Ottestad L, Lund E, Johannessen J: Neuron-specific enolase positive breast carcinomas. Histol Histopathol 1988, 3:97-102.
• [16]Matsushima S, Mori M, Adachi Y, Matsukuma A, Sugimachi K: S100 protein positive human breast carcinomas: an immunohistochemical study. J Surg Oncol 1994, 55:108-113.
• [17]Sens DA, Park S, Gurel V, Sens MA, Garrett SH, Somji S: Inorganic cadmium- and arsenite-induced malignant transformation of human bladder urothelial cells. Toxicol Sci 2004, 79:56-63.
• [18]Cao L, Zhou XD, Sens MA, Garrett SH, Zheng Y, Dunlevy JR, Sens DA, Somji S: Keratin 6 expression correlates to areas of squamous differentiation in multiple independent isolates of As+3- induced bladder cancer. J Appl Toxicol 2010, 30:416-430.
• [19]Somji S, Zhou XD, Mehus A, Sens MA, Garrett SH, Lutz KL, Dunlevy JR, Zheng Y, Sens DA: Variation of keratin 7 expression and other phenotypic characteristics of independent isolates of cadmium transformed human urothelial cells (UROtsa). Chem Res Toxicol 2010, 23:348-356.
• [20]Somji S, Garrett SH, Zhou XD, Zheng Y, Sens DA, Sens MA: Absence of metallothionein 3 expression in breast cancer is a rare, but favorable marker of outcome that is under epigenetic control. Toxicol Environ Chem 2010, 92:1673-1695.
• [21]Pancholi V: Multifunctional α-enolase: its role in diseases. Cell Mol Life Sci 2001, 58:902-920.
• [22]Capello M, Ferri-Borgogno S, Cappello P, Novelli F: α-enolase: a promising therapeutic and diagnostic tumor target. FEBS J 2011, 278:1064-1074.
• [23]Lung J, Liu KJ, Chang JY, Leu SJ, Shih NY: MBP-1 is efficiently encoded by an alternate transcript of the ENO1 gene but post-translationally regulated by proteasome-dependent protein turnover. FEBS J 2010, 277:4308-4321.
• [24]Benbrahim-Tallaa L, Tokar EJ, Diwan BA, Dill AL, Coppin JF, Waalkes MP: Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype. Environ Hlth Perspect 2009, 117:1847-1852.
• [25]Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ: Purification and unique properties of mammary epithelial stem cells. Nature 2006, 439:993-997.
• [26]Tokar EJ, Weber MM: Cholecalciferol (vitamin D3) inhibits growth and invasion by up-regulating nuclear receptors and 25-hydroxylase (CYP27A1) in human prostate cancer cells. Clin Exp Metastasis 2005, 22:275-284.
• [27]Weiler E, Benali A: Olfactory epithelia differentially express neuronal markers. J Neurocytol 2005, 34:217-240.
• [28]Loja T, Chlapek P, Kuglik P, Pesakova M, Oltova A, Cejpek P, Veselska R: Characterization of a GM7 glioblastoma cell line showing CD+2133 positivity and both cytoplasmic and nuclear localization of nestin. Oncol Reports 2009, 21:119-127.
• [29]Miremadi A, Pinder SE, Lee AHS, Bell JA, Paish EC, Wencyk P, Elston CW, Nicholson RI, Blamey RW, Robertson JF, Ellis IO: Neuroendocrine differation and prognosis in breast carcinoma. Histopathol 2002, 40:215-222.
• [30]Makretsov N, Gilks CB, Coldman AJ, Hayes M, Huntsman D: Tissue microarray analysis of neuroendocrine differentiation and its prognostic significance in breast cancer. Hum Pathol 2003, 34:1001-1008.
• [31]Sapino A, Bussolati G: Is detection of endocrine cells in breast adenocarcinoma of diagnostic and clinical significance? Histopathol 2002, 40:211-214.
• [32]Sawaki M, Yokoi K, Nagasaka T, Watanabe R, Kagawa C, Takada H, Sato S, Yamada T, Kirumori T, Imai T, Nakao A: Prognostic importance of neuroendocrine differentiation in Japanese breast cancer patients. Surg Today 2010, 40:831-835.
• [33]Hao X, Sun B, Hu L, Lahdesmaki H, Dunmire V, Feng Y, Zhang SW, Wang H, Wu C, Wang H, Fuller GN, Symmans WF, Zhang W: Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis. Cancer 2004, 100:1110-1122.
• [34]Abba MC, Hu Y, Sun H, Drake JA, Gaddis S, Baggerly K, Sahin A, Aldaz CM: Gene expression signature of estrogen receptor α status in breast cancer. BMC Genomics 2005, 6:37. BioMed Central Full Text
• [35]Iavicoli I, Fontana L, Bergamaschi A: The effects of metals as endocrine disruptors. J Toxicol Environ Hlth B 2009, 12:206-223.
• [36]Davey JC, Bodwell JE, Gosse JA, Hamilton JW: Arsenic as an endocrine disruptor: effects of arsenic on estrogen receptor-mediated gene expression in vivo and in cell culture. Toxicol Sci 2007, 98:75-86.
• [37]Rossi MR, Somji S, Garrett SH, Sens MA, Nath J, Sens DA: Expression of hsp 27, hsp 60, hsc 70 and hsp 70 stress response genes in cultured human urothelial cells (UROtsa) exposed to lethal and sublethal concentrations of sodium arsenite. Environ Health Perspect 2002, 110:1225-1232.
• [38]San RHC, Laspia MF, Soiefer AI, Maslansky CJ, Rice JM, Williams GM: A survey of growth in soft agar and cell surface properties as markers for transformation in adult rat liver epithelial-like cell cultures. Cancer Res 1979, 39:1026-1034.
• [39]Gurel V, Sens DA, Somji S, Garrett SH, Weiland T, Sens MA: Post-transcriptional regulation of metallothionein isoform 1 and 2 expression in the human breast and the MCF-10A cell line. Toxicol Sci 2005, 85:906-915.