Objective: The purpose of the study was to evaluate clinical presentation of breast cancer anti-estrogen resistance protein 1 (BCAR1, also known as p130cas) expression in pulmonary diseases, and to assess its potential as a molecular marker for diagnosis and prognosis.
Methods: Between March 2008 and August 2010, we enrolled a total of 80 patients (group A) with non-small-cell lung cancer (NSCLC), 48 patients (group B) with pulmonary tuberculosis (including 27 cases of tuberculoma and 21 cases of cavitary pulmonary tuberculosis), and 32 patients (group C) with other benign pulmonary mass (hamartoma in 15 cases, inflammatory pseudotumor in 10 cases, fibroid tumor in 7 cases). Additionally, 160 healthy age- and sex-matched volunteers were recruited as healthy controls. Tissue BCAR1 expression was investigated by using tissue microarray and immunohistochemistry. BCAR1 and tumor markers (carcinoma embryonic antigen [CEA] and the cancer antigens CA19-9 and CA125) in serum were assayed by using ELISA and immunoradiometrics, respectively.
Results: BCAR1 expression was detected (either in the nucleus, the cytoplasm, or both) in tumor cells in 79 of the 80 NSCLC cases in group A, and in fibroblasts in 41 of the 48 pulmonary tuberculosis cases in group B. However, it was not detected in the normal adjacent tissue in 70 of the 80 cases in group A and in 47 of the 48 cases in group B. In group C, BCAR1 expression was negative in all 32 cases. Additionally, we investigated adjacent tissue with acute or chronic inflammation in 20 cases from group C, and found no expression of BCAR1. Serum BCAR1 levels were significantly higher in patients with NSCLC than in the control group, increased gradually with the progression of tumor staging, and decreased after removal of the tumors. The levels were significantly lower in bronchioloalveolar carcinoma than in other subtypes of carcinoma (Mann-Whitney U test, Z = −5.089; p<0.001). Serum BCAR1 levels were significantly higher in patients with pulmonary tuberculosis than in the control group, were positively and significantly correlated with the diameter of the tuberculosis lesion (Spearman’s rho, correlation coefficient 0.753; p< 0.001), and decreased after removal of the tuberculosis lesions. The levels were significantly higher in patients with cavitary pulmonary tuberculosis than in those with tuberculoma (517.6 ± 326.5 vs 282.2±137.6; Student’s t-test, t =−3.387; p = 0.001). In group C, there was no appreciable difference in serum BCAR1 levels compared with the matched controls (222.8 ± 111.0 vs 201.6 ± 35.7; Dunnett’s T3 test, p = 0.993). The discrimination power of combining BCAR1 and tumor markers in NSCLC versus benign lung diseases was higher than that of sole use of BCAR1 as a marker (maximal sum of sensitivity and specificity: 1.538 vs 1.237).
Conclusion: We conclude that a combined assay of serum BCAR1 and traditional tumor markers is potentially applicable for distinguishing NSCLC from benign lung diseases. However, the clinical utility of serum BCAR1 as a molecular marker for prognosis in NSCLC or pulmonary tuberculosis requires further clarification and verification.
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Reynolds AB, Roesel DJ, Kanner SB, et al. Transformation-specific tyrosine phosphorylation of a novel cellular protein in chicken cells expressing oncogenic variants of the avian cellular src gene. Mol Cell Biol 1989; 9: 629–38
Kanner SB, Reynolds AB, Parsons JT. Tyrosine phosphorylation of a 120-kilodalton pp60src substrate upon epidermal growth factor and platelet-derived growth factor receptor stimulation and in polyomavirus middle-T-antigen-transformed cells. Mol Cell Biol 1991; 11: 713–20
Zhao Y, Min C, Vora SR, et al. The lysyl oxidase pro-peptide attenuates fibronectin-mediated activation of focal adhesion kinase and p130Cas in breast cancer cells. J Biol Chem 2009; 284: 1385–93
Schrecengost RS, Riggins RB, Thomas KS, et al. Breast cancer antiestrogen resistance-3 expression regulates breast cancer cell migration through promotion of p130Cas membrane localization and membrane ruffling. Cancer Res 2007; 67: 6174–82
Cabodi S, Tinnirello A, Di Stefano P, et al. p130Cas as a new regulator of mammary epithelial cell proliferation, survival, and HER2-neu oncogene-dependent breast tumorigenesis. Cancer Res 2006; 66: 4672–80
Tikhmyanova N, Little JL, Golemis EA. CAS proteins in normal and pathological cell growth control. Cell Mol Life Sci 2010; 67: 1025–48
Dorssers LCJ, Grebenchtchikov N, Brinkman A, et al. The prognostic value of BCAR1 in patients with primary breast cancer. Clin Cancer Res 2004; 10: 6194–202
Ta HQ, Thomas KS, Schrecengost RS, et al. A novel association between p130Cas and resistance to the chemotherapeutic drug Adriamycin in human breast cancer cells. Cancer Res 2008; 68: 8796–804
van der Flier S, Brinkman A, Look MP, et al. Bcar1/p130Cas protein and primary breast cancer: prognosis and response to tamoxifen treatment. J Natl Cancer Inst 2000; 92: 120–7
Guo C, Liu QG, Yang W, et al. Relation among p130Cas, E-cadherin and beta-catenin expression, clinicopathologic significance and prognosis in human hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 2008; 7: 490–6
Frankel P, Pellet-Many C, Lehtolainen P, et al. Chondroitin sulphate-modified neuropilin 1 is expressed in human tumour cells and modulates 3D invasion in the U87MG human glioblastoma cell line through a p130Cas-mediated pathway. EMBO Rep 2008; 9: 983–9
Fromont G, Vallancien G, Validire P, et al. BCARI expression in prostate cancer: association with 16q23 LOH status, tumor progression and EGFR/KAI1 staining. Prostate 2007; 67: 268–73
Beinke C, Van Beuningen D, Cordes N. Ionizing radiation modules of the expression and tyrosine phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK) and its substrates p130cas and paxillin in A549 human lung carcinoma cells in vitro. Int J Radiat Biol 2003; 79: 721–31
Wei L, Yang Y, Zhang X, et al. Anchorage-independent phosphorylation of p130(Cas) protects lung adenocarcinoma cells from anoikis. J Cell Biochem 2002; 87: 439–49
Viboud GI, Bliska JB. Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 2005; 59: 69–89
Defilippi P, Di Stefano P, Cabodi S. p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol 2006; 16: 257–63
Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging system for lung cancer. Ann Thorac Cardiovasc Surg 2009; 15(1): 4–9
Manie SN, Beck AR, Astier A, et al. Involvement of p130(Cas) and p105(HEF1), a novel Cas-like docking protein, in a cytoskeleton-dependent signaling pathway initiated by ligation of integrin or antigen receptor on human B cells. J Biol Chem 1997; 272: 4230–6
Wendt MK, Smith JA, Schiemann WP. p130Cas is required for mammary tumor growth and transforming growth factor-beta-mediated metastasis through regulation of Smad2/3 activity. J Biol Chem 2009; 284: 34145–56
Zouq NK, Keeble JA, Lindsay J, et al. FAK engages multiple pathways to maintain survival of fibroblasts and epithelia: differential roles for paxillin and p130Cas. J Cell Sci 2009; 122: 357–67
Breathnach OS, Kwiatkowski DJ, Finkelstein DM, et al. Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease. J Thorac Cardiovasc Surg 2001; 121: 42–7
Liu YY, Chen YM, Huang MH, et al. Prognosis and recurrent patterns in bronchioloalveolar carcinoma. Chest 2000; 118: 940–7
Shi J, Casanova JE. Invasion of host cells by Salmonella typhimurium requires focal adhesion kinase and p130Cas. Mol Biol Cell 2006; 17: 4698–708
Wallis RS, Doherty TM, Onyebujoh P, et al. Biomarkers for tuberculosis disease activity, cure, and relapse. Lancet Infect Dis 2009; 9: 162–72
Apt AS, Kondrat’eva TK. Tuberculosis: pathogenesis, immune responses and genetics of the host. Mol Biol (Mosk) 2008; 42: 880–90
Yoder MA, Lamichhane G, Bishai WR. Cavitary pulmonary tuberculosis: the Holy Grail of disease transmission. Curr Sci 2004; 86: 74–81
Ralph AP, Ardian M, Wiguna A, et al. A simple, valid, numerical score for grading chest x-ray severity in adult smear-positive pulmonary tuberculosis. Thorax 2010; 65: 863–9
Smirnov GA, Ravdel GD, Fattakhova RM, et al. Outcome of pulmonary tuberculosis with single destructive cavity depending on its size [in Russian]. Probl Tuberk 1990; 2: 26–9
The authors wish it to be known publicly that the first two authors (Bo Deng and Wei Huang) should be regarded as joint first authors. We appreciate the editorial board and all the anonymous reviewers for their excellent comments and suggestions that improved our study greatly.
No funding has been received for the conduct of this study or the preparation of this manuscript. The authors have no conflicts of interest that are directly related to the content of this study.
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Deng, B., Huang, W., Tan, Q. et al. Breast Cancer Anti-Estrogen Resistance Protein 1 (BCAR1/p130cas) in Pulmonary Disease Tissue and Serum. Mol Diagn Ther 15, 31–40 (2011). https://doi.org/10.1007/BF03257191
- Receiver Operating Characteristic Curve
- Focal Adhesion Kinase
- Pulmonary Tuberculosis
- Normal Adjacent Tissue
- Matched Control Group