title: Detection of Brk expression in non-small cell lung cancer: clinicopathological relevance.
abstract: Breast tumor kinase (Brk), also known as protein tyrosine kinase 6, is a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. Brk upregulation and oncogenic properties have been found in several malignant tumors, including breast, colon carcinomas, and melanomas, but the expression of Brk and its clinical significance in non-small cell lung cancer (NSCLC) remains unclear. In the current study, we examined the expression of Brk and its correlation with clinicopathological features involving p53, ki67, and E-cadherin status in NSCLC tissue using immunohistochemistry. We also used immunocytochemistry and immunofluorescent staining to examine the Brk expression and its subcellular localization in NSCLC cell lines, including LTE and H460. We further confirmed cytoplasmic and nucleus expression of Brk in LTE and H460 cells using Western blotting. The Brk expression in NSCLC cells was mainly found in cytoplasm (59/122, 48.4%) with some nucleus staining (17/122, 13.9%) with a total positive rate of 53.3% (65/122). Cytoplasmic Brk expression in NSCLC was higher than that in normal lung tissues (24/122, 19.7%) (P < 0.05). Increased cytoplasmic Brk expression in NSCLC was associated with large tumor size (≥ 3 cm), lymph node metastasis, and advanced tumor-node-metastasis (TNM) stages (III and IV) (P < 0.05). Moreover, increased cytoplasmic Brk expression was positively associated with Ki67 status in NSCLC (P < 0.05). Reduced E-cadherin expression was also found to be associated with lymph node metastasis and advanced TNM stages (III and IV) in NSCLC (P < 0.05). Brk expression was not associated with E-cadherin expression and P53 status in NSCLC (P > 0.05). The present findings indicate an increase of cytoplasmic Brk expression in NSCLC which may play a role in tumor development, including tumor expansion and lymph node metastasis in which Ki67, but not E-cadherin, and P53 status may be involved.
authors: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, 110001, Shenyang, China. fanchuifeng@yeah.net
authors: Chuifeng
authors: C
authors: Fan
authors: Yang
authors: Y
authors: Zhao
authors: Di
authors: D
authors: Liu
authors: Xiupeng
authors: X
authors: Zhang
authors: Enhua
authors: E
authors: Wang
references: Oncogene. 2003 Aug 7;22(32):5006-10
references: 12902983
references: Oncogene. 1994 Aug;9(8):2383-90
references: 8036022
references: J Biol Chem. 2005 Nov 18;280(46):38639-47
references: 16179349
references: J Biochem. 2009 Jul;146(1):133-9
references: 19304789
references: Cancer Sci. 2011 Apr;102(4):756-61
references: 21205088
references: Clin Cancer Res. 1999 Jul;5(7):1767-77
references: 10430081
references: Oncogene. 2003 Jul 3;22(27):4212-20
references: 12833144
references: Mol Cell Biol. 2004 Dec;24(24):10558-72
references: 15572663
references: Oral Oncol. 2004 Nov;40(10):1040-7
references: 15509496
references: J Biol Chem. 1997 Feb 7;272(6):3129-32
references: 9013542
references: Br J Dermatol. 2005 Aug;153(2):282-9
references: 16086737
references: Oncogene. 1995 Jan 19;10(2):349-57
references: 7838533
references: Cell Signal. 2008 Feb;20(2):432-42
references: 18077133
references: Cancer Res. 2008 Oct 1;68(19):7779-87
references: 18829532
references: Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14477-82
references: 9405638
references: Oncogene. 1997 Aug 14;15(7):799-805
references: 9266966
references: Int J Cancer. 1997 Jun 11;71(6):1061-5
references: 9185712
references: Oncogene. 1994 Jul;9(7):2053-7
references: 8208550
references: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12463-8
references: 18719096