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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

CA1 contributes to microcalcification and tumourigenesis in breast cancer

Authors: Yabing Zheng, Bing Xu, Yan Zhao, He Gu, Chang Li, Yao Wang, Xiaotian Chang

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Although mammary microcalcification is frequently observed and has been associated with poor survival in patients with breast cancer, the genesis of calcification remains unclear. Carbonic anhydrase I (CA1) has been shown to promote calcification by catalysing the hydration of CO2. This study aimed to determine whether CA1 was correlated with microcalcification and with other processes that are involved in breast cancer tumourigenesis.

Methods

CA1 expression in breast cancer tissues and blood samples was detected using western blotting, real-time PCR, immunohistochemistry and ELISA. Calcification was induced in the cultured 4T1 cell line originating from mouse breast tumours, using ascorbic acid and β-glycerophosphate. Acetazolamide, a chemical inhibitor of CA1, was also added to the culture to determine the role of CA1 in calcification. The MCF-7 human breast cancer cell line was treated with anti-CA1 siRNA and was assessed using a CCK-8 cell proliferation assay, an annexin V cell apoptosis assay, transwell migration assay and a human breast cancer PCR array. The tag SNP rs725605, which is located in the CA1 locus, was genotyped using TaqMan® genotyping.

Results

Increased CA1 expression was detected in samples of breast carcinoma tissues and blood obtained from patients with breast cancer. A total of 15.3 % of these blood samples exhibited a 2.1-fold or higher level of CA1 expression, compared to the average level of CA1 expression in samples from healthy controls. Following the induction of calcification of 4T1 cells, both the number of calcium-rich deposits and the expression of CA1 increased, whereas the calcification and CA1 expression were significantly supressed in the presence of acetazolamide. Increased migration and apoptosis were observed in MCF-7 cells that were treated with anti-CA1 siRNA. The PCR array detected up-regulation of the androgen receptor (AR) and down-regulation of X-box binding protein 1 (XBP1) in the treated MCF-7 cells. Significant differences in the allele and genotype frequencies of rs725605 were detected in the cohort of patients with breast cancer but not in other tumours.

Conclusion

The results of this study suggested that CA1 is a potential oncogene and that it contributes to abnormal cell calcification, apoptosis and migration in breast cancer.
Appendix
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Literature
1.
Morgan M, Cooke M, McCarthy G. Microcalcifications associated with breast cancer: an epiphenomenon or biologically significant feature of selected tumors? J Mammary Gland Biol Neoplasia. 2005;10(2):181–7.CrossRefPubMed
2.
Frappart L, Boudeulle M, Boumendil J, Lin H, Martinon I, Palayer C, et al. Structure and composition of microcalcifications in benign and malignant lesions of the breast: study by light microscopy, transmission and scanning electron microscopy, microprobe analysis, and X-ray diffraction. Hum Pathol. 1984;15(9):880–9.
3.
Haka A, Shafer-Peltier K, Fitzmaurice M, Crowe J, Dasari R, Feld M. Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy. Cancer Res. 2002;62(18):5375–80.PubMed
4.
Owen TA, Aronow M, Shalhoub V, Barone L, Wilming L, Tassinari M, et al. Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. J Cell Physiol. 1990;143(3):420–30.
5.
6.
Ripamonti U, Crooks J, Khoali L, Roden L. The induction of bone formation by coral-derived calcium carbonate/hydroxyapatite constructs. Biomaterials. 2009;30(7):1428–39.CrossRefPubMed
7.
Damien C, Ricci J, Christel P, Alexander H, Patat JL. Formation of a calcium phosphate-rich layer on absorbable calcium carbonate bone graft substitutes. Calcif Tissue Int. 1994;55:151–8.CrossRefPubMed
8.
9.
Parissa M, Koorosh A, Nader M. Investigating the application of enzyme carbonic anhydrase for CO2 sequestration purposes. Ind Eng Chem Res. 2007;46(3):921–6.CrossRef
10.
Ramanan R, Kannan K, Sivanesan S. Bio-sequestration of carbon dioxide using carbonic anhydrase enzyme purified from Citrobacter freundii. World J Microbiol Biotechnol. 2009;25(6):981–7.CrossRef
11.
Chang X, Zheng Y, Yang Q, Wang L, Pan J, Xia Y, et al. Carbonic anhydrase I (CA1) is involved in the process of bone formation and is susceptible to ankylosing spondylitis. Arthritis Res Ther. 2012;14(4):R176. doi:10.​1186/​ar3929.
12.
13.
14.
Cox R, Hernandez-Santana A, Ramdass S, McMahon G, Harmey JH, Morgan MP. Microcalcifications in breast cancer: novel insights into the molecular mechanism and functional consequence of mammary mineralisation. Br J Cancer. 2012;106(3):525–37. doi: 10.​1038/​bjc.​2011.​583.
15.
16.
17.
Hall GE, Kenny AD. Role of carbonic anhydrase in bone resorption induced by 1,25 dihydroxyvitamin D3 in vitro. Calcif Tissue Int. 1985;37(2):134–42.CrossRefPubMed
18.
Hall GE, Kenny AD. Role of carbonic anhydrase in bone resorption induced by prostaglandin E2 in vitro. Pharmacology. 1985;30(6):339–47.CrossRefPubMed
19.
Thouverey C, Strzelecka-Kiliszek A, Balcerzak M, Buchet R, Pikula S. Matrix vesicles originate from apical membrane microvilli of mineralizing osteoblast-like Saos-2 cells. J Cell Biochem. 2009;106(1):127–38. doi:10.​1002/​jcb.​21992.CrossRefPubMed
20.
21.
Brinkmann A, Faber P, van Rooij H, Kuiper G, Ris C, Klaassen P, et al. The human androgen receptor: domain structure, genomic organization and regulation of expression. J Steroid Biochem. 1989;34(1-6):307–10.
22.
Hu R, Dawood S, Holmes M, Collins L, Schnitt S, Cole K, et al. Androgen receptor expression and breast cancer survival in postmenopausal women. Clin Cancer Res. 2011;17(7):1867–74. doi:10.​1158/​1078-0432.​CCR-10-2021.
23.
Park S, Koo J, Kim M, Park H, Lee J, Lee J, et al. Androgen receptor expression is significantly associated with better outcomes in estrogen receptor-positive breast cancers. Ann Oncol. 2011;22(8):1755–62. doi:10.​1093/​annonc/​mdq678.
24.
Agoff S, Swanson P, Linden H, Hawes S, Lawton T. Androgen receptor expression in estrogen receptor-negative breast cancer. Immunohistochemical, clinical, and prognostic associations. Am J Clin Pathol. 2003;120(5):725–31.CrossRefPubMed
25.
Yeh S, Hu Y, Wang P, Xie C, Xu Q, Tsai M, et al. Abnormal mammary gland development and growth retardation in female mice and MCF7 breast cancer cells lacking androgen receptor. Exp Med. 2003;198(12):1899–908.
26.
Venken K, De Gendt K, Boonen S, Ophoff J, Bouillon R, Swinnen J, et al. Relative impact of androgen and estrogen receptor activation in the effects of androgens on trabecular and cortical bone in growing male mice: a study in the androgen receptor knockout mouse model. J Bone Miner Res. 2006;21(4):576–85.
27.
Kang H, Shyr C, Huang C, Tsai M, Orimo H, Lin P, et al. Altered TNSALP expression and phosphate regulation contribute to reduced mineralization in mice lacking androgen receptor. Mol Cell Biol. 2008;28(24):7354–67. doi:10.​1128/​MCB.​00582-08.
28.
Reimold A, Etkin A, Clauss I, Perkins A, Friend D, Zhang J, et al. An essential role in liver development for transcription factor XBP-1. Genes Dev. 2000;14(2):152–7.
29.
Davies M, Barraclough D, Stewart C, Joyce K, Eccles R, Barraclough R, et al. Expression and splicing of the unfolded protein response gene XBP-1 are significantly associated with clinical outcome of endocrine-treated breast cancer. Int J Cancer. 2008;123(1):85–8. doi:10.​1002/​ijc.​23479.
30.
Reimold A, Iwakoshi N, Manis J, Vallabhajosyula P, Szomolanyi-Tsuda E, Gravallese EM, et al. Plasma cell differentiation requires the transcription factor XBP-1. Nature. 2001;412(6844):300–7.
31.
32.
Gálfi P, Neogrády Z, Csordás A. Apoptosis sensitivity is not correlated with sensitivity to proliferation inhibition by the histone deacetylase inhibitors butyrate and TSA. Cancer Lett. 2002;188(1-2):141–52.CrossRefPubMed
33.
Zarif J, Lamb L, Schulz V, Nollet E, Miranti C. Androgen receptor non-nuclear regulation of prostate cancer cell invasion mediated by Src and matriptase. Oncotarget. 2015;6(9):6862–76.CrossRefPubMedPubMedCentral
34.
Zhang Y, Pan T, Zhong X, Cheng C. Androgen receptor promotes esophageal cancer cell migration and proliferation via matrix metalloproteinase 2. Tumour Biol. 2015;28.
35.
Termuhlen P, Sweeney-Gotsch B, Berman R, Ellis L, Bucana C, Shen Y, et al. Increased apoptosis in metastatic human colonic adenocarcinomas. Cancer Biol Ther. 2002;1(1):58–63.
36.
37.
Bellahcène A, Castronovo V. Expression of bone matrix proteins in human breast cancer: potential roles in microcalcification formation and in the genesis of bone metastases. Bull Cancer. 1997;84(1):17–24.PubMed
38.
Morgan M, Cooke M, Christopherson P, Westfall P, McCarthy G. Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines. Mol Carcinog. 2001;32(3):111–7.CrossRefPubMed
Metadata
Title
CA1 contributes to microcalcification and tumourigenesis in breast cancer
Authors
Yabing Zheng
Bing Xu
Yan Zhao
He Gu
Chang Li
Yao Wang
Xiaotian Chang
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1707-x

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