FAK overexpression and p53 mutations are highly correlated in human breast cancer

被引:69
作者
Golubovskaya, Vita M. [1 ]
Conway-Dorsey, Kathleen [2 ,3 ]
Edmiston, Sharon N. [2 ,3 ]
Tse, Chiu-Kit [2 ,3 ]
Lark, Amy A. [4 ]
Livasy, Chad A. [5 ]
Moore, Dominic [3 ,6 ]
Millikan, Robert C. [2 ,3 ]
Cance, William G. [1 ]
机构
[1] Roswell Pk Canc Inst, Dept Surg Oncol, Buffalo, NY 14263 USA
[2] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA
[3] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
[4] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[5] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA
[6] Univ N Carolina, Dept Stat, Chapel Hill, NC 27599 USA
关键词
p53; focal adhesion kinase; breast cancer; tumor; FOCAL ADHESION KINASE; BINDING-SITES; EXPRESSION; CARCINOMAS; SURVIVAL; CELLS; GENE;
D O I
10.1002/ijc.24486
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Focal adhesion kinase (FAK) is overexpressed in a number of tumors, including breast cancer. Another marker of breast cancer tumorigenesis is the tumor suppressor gene p53 that is frequently mutated in breast cancer. In the present study, our aim was to find a correlation between FAK overexpression, p53 expression and mutation status in a population-based series of invasive breast cancer tumors from the Carolina Breast Cancer Study. Immunohistochemical analyses of 622 breast cancer tumors revealed that expression of FAK and p53 were highly correlated (p = 0.0002) and FAK positive tumors were 1.8 times more likely to be p53 positive compared to FAK negative tumors [odds ratio (OR) = 1.8; 95% Confidence Interval (CI) 1.2-2.8, adjusted for age, race and stage at diagnosis]. Tumors positive for p53 expression showed higher intensity of FAK staining (p < 0.0001) and higher percent of FAK positive staining (p < 0.0005). From the same study, we evaluated 596 breast tumors for mutations in the p53 gene, using single strand conformational polymorphism and sequencing. Statistical analyses were performed to determine the correlation between p53 mutation status and FAK expression in these tumors. We found that FAK expression and p53 mutation were positively correlated (p < 0.0001) and FAK positive tumors were 2.5 times more likely to be p53 mutation positive compared to FAK negative tumors [adjusted OR = 2.5, 95% CI 1.6-3.9]. This is the first analysis demonstrating a high correlation between FAK expression and p53 mutations in a population-based series of breast tumors. (C) 2009 UICC
引用
收藏
页码:1735 / 1738
页数:4
相关论文
共 19 条
[1]  
Cance WG, 2000, CLIN CANCER RES, V6, P2417
[2]   Focal Adhesion Kinase Versus p53: Apoptosis or Survival? [J].
Cance, William G. ;
Golubovskaya, Vita M. .
SCIENCE SIGNALING, 2008, 1 (20) :pe22
[3]  
Conway K, 2002, CANCER RES, V62, P1987
[4]  
Fukushima T, 1995, Eur J Surg Oncol, V21, P595, DOI 10.1016/S0748-7983(95)95047-8
[5]   The complexity of p53 modulation: emerging patterns from divergent signals [J].
Giaccia, AJ ;
Kastan, MB .
GENES & DEVELOPMENT, 1998, 12 (19) :2973-2983
[6]   Cloning and characterization of the promoter region of human focal adhesion kinase gene: nuclear factor kappa B and p53 binding sites [J].
Golubovskaya, V ;
Kaur, A ;
Cance, W .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2004, 1678 (2-3) :111-125
[7]   P53 regulates FAK expression in human tumor cells [J].
Golubovskaya, Vita M. ;
Finch, Richard ;
Kweh, Frederick ;
Massoll, Nicole A. ;
Campbell-Thompson, Martha ;
Wallace, Margaret R. ;
Cance, William G. .
MOLECULAR CARCINOGENESIS, 2008, 47 (05) :373-382
[8]   Focal adhesion kinase and p53 signaling in cancer cells [J].
Golubovskaya, Vita M. ;
Cance, William G. .
INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 263, 2007, 263 :103-+
[9]   Focal adhesion kinase signaling activities and their implications in the control of cell survival and motility [J].
Hanks, SK ;
Ryzhova, L ;
Shin, NY ;
Brábek, J .
FRONTIERS IN BIOSCIENCE-LANDMARK, 2003, 8 :D982-D996
[10]  
ILIC D, 2005, J BIOL CHEM, V280, P25008