Literature DB >> 19521985

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

Vita M Golubovskaya1, Kathleen Conway-Dorsey, Sharon N Edmiston, Chiu-Kit Tse, Amy A Lark, Chad A Livasy, Dominic Moore, Robert C Millikan, William G Cance.   

Abstract

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.

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Year:  2009        PMID: 19521985      PMCID: PMC2773794          DOI: 10.1002/ijc.24486

Source DB:  PubMed          Journal:  Int J Cancer        ISSN: 0020-7136            Impact factor:   7.396


  20 in total

1.  A global map of p53 transcription-factor binding sites in the human genome.

Authors:  Chia-Lin Wei; Qiang Wu; Vinsensius B Vega; Kuo Ping Chiu; Patrick Ng; Tao Zhang; Atif Shahab; How Choong Yong; YuTao Fu; Zhiping Weng; JianJun Liu; Xiao Dong Zhao; Joon-Lin Chew; Yen Ling Lee; Vladimir A Kuznetsov; Wing-Kin Sung; Lance D Miller; Bing Lim; Edison T Liu; Qiang Yu; Huck-Hui Ng; Yijun Ruan
Journal:  Cell       Date:  2006-01-13       Impact factor: 41.582

2.  Nuclear FAK promotes cell proliferation and survival through FERM-enhanced p53 degradation.

Authors:  Ssang-Taek Lim; Xiao Lei Chen; Yangmi Lim; Dan A Hanson; Thanh-Trang Vo; Kyle Howerton; Nicholas Larocque; Susan J Fisher; David D Schlaepfer; Dusko Ilic
Journal:  Mol Cell       Date:  2008-01-18       Impact factor: 17.970

3.  p53 mutations and overexpressions in Japanese breast cancer.

Authors:  T Fukushima; M Onda; R Abe; T Otake; I Kimijima; A Tsuchiya
Journal:  Eur J Surg Oncol       Date:  1995-12       Impact factor: 4.424

4.  High focal adhesion kinase expression in invasive breast carcinomas is associated with an aggressive phenotype.

Authors:  Amy L Lark; Chad A Livasy; Lynn Dressler; Dominic T Moore; Robert C Millikan; Joseph Geradts; Mary Iacocca; David Cowan; Debbie Little; Rolf J Craven; William Cance
Journal:  Mod Pathol       Date:  2005-10       Impact factor: 7.842

5.  Upregulation of focal adhesion kinase (FAK) expression in ductal carcinoma in situ (DCIS) is an early event in breast tumorigenesis.

Authors:  Harry M Lightfoot; Amy Lark; Chad A Livasy; Dominic T Moore; David Cowan; Lynn Dressler; Rolf J Craven; William G Cance
Journal:  Breast Cancer Res Treat       Date:  2004-11       Impact factor: 4.872

6.  Focal adhesion kinase overexpression in endometrial neoplasia.

Authors:  Chad A Livasy; Dominic Moore; William G Cance; Ruth A Lininger
Journal:  Appl Immunohistochem Mol Morphol       Date:  2004-12

7.  Direct interaction of the N-terminal domain of focal adhesion kinase with the N-terminal transactivation domain of p53.

Authors:  Vita M Golubovskaya; Richard Finch; William G Cance
Journal:  J Biol Chem       Date:  2005-04-25       Impact factor: 5.157

8.  Expression of focal adhesion kinase gene and invasive cancer.

Authors:  T M Weiner; E T Liu; R J Craven; W G Cance
Journal:  Lancet       Date:  1993-10-23       Impact factor: 79.321

Review 9.  Focal adhesion kinase and p53 signaling in cancer cells.

Authors:  Vita M Golubovskaya; William G Cance
Journal:  Int Rev Cytol       Date:  2007

10.  Extracellular matrix survival signals transduced by focal adhesion kinase suppress p53-mediated apoptosis.

Authors:  D Ilić; E A Almeida; D D Schlaepfer; P Dazin; S Aizawa; C H Damsky
Journal:  J Cell Biol       Date:  1998-10-19       Impact factor: 10.539

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  45 in total

1.  Nanog increases focal adhesion kinase (FAK) promoter activity and expression and directly binds to FAK protein to be phosphorylated.

Authors:  Baotran Ho; Gretchen Olson; Sheila Figel; Irwin Gelman; William G Cance; Vita M Golubovskaya
Journal:  J Biol Chem       Date:  2012-04-05       Impact factor: 5.157

2.  Tumor Necrosis Factor-α (TNFα)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death.

Authors:  María José Hernández-Corbacho; Daniel Canals; Mohamad M Adada; Mengling Liu; Can E Senkal; Jae Kyo Yi; Cungui Mao; Chiara Luberto; Yusuf A Hannun; Lina M Obeid
Journal:  J Biol Chem       Date:  2015-08-28       Impact factor: 5.157

Review 3.  Targeting the p53 pathway.

Authors:  Vita M Golubovskaya; William G Cance
Journal:  Surg Oncol Clin N Am       Date:  2013-07-30       Impact factor: 3.495

4.  Down-regulation of ALDH1A3, CD44 or MDR1 sensitizes resistant cancer cells to FAK autophosphorylation inhibitor Y15.

Authors:  Vita Golubovskaya; Shalana O'Brien; Baotran Ho; Melissa Heffler; Jeffrey Conroy; Quang Hu; Dan Wang; Song Liu; William G Cance
Journal:  J Cancer Res Clin Oncol       Date:  2015-02-06       Impact factor: 4.553

5.  Interaction between p53 codon 72 and MDM2 309T>G polymorphisms and the risk of hepatocellular carcinoma.

Authors:  Moqin Qiu; Yingchun Liu; Xiangyuan Yu; Linyuan Qin; Chunhua Bei; Xiaoyun Zeng; Xiaoqiang Qiu; Bo Tang; Songqing He; Hongping Yu
Journal:  Tumour Biol       Date:  2015-10-17

6.  The microarray gene profiling analysis of glioblastoma cancer cells reveals genes affected by FAK inhibitor Y15 and combination of Y15 and temozolomide.

Authors:  Grace Huang; Baotran Ho; Jeffrey Conroy; Song Liu; Hu Qiang; Vita Golubovskaya
Journal:  Anticancer Agents Med Chem       Date:  2014-01       Impact factor: 2.505

7.  Overexpression of CD155 relates to metastasis and invasion in osteosarcoma.

Authors:  Baobiao Zhuo; Yuan Li; Feng Gu; Zhengwei Li; Qingzeng Sun; Yingchun Shi; Yang Shen; Fengfei Zhang; Rong Wang; Xiaodong Wang
Journal:  Oncol Lett       Date:  2018-03-09       Impact factor: 2.967

Review 8.  Bi-directional signaling: extracellular matrix and integrin regulation of breast tumor progression.

Authors:  Scott Gehler; Suzanne M Ponik; Kristin M Riching; Patricia J Keely
Journal:  Crit Rev Eukaryot Gene Expr       Date:  2013       Impact factor: 1.807

9.  Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population.

Authors:  Mang Xiao; Lei Zhang; Xinhua Zhu; Jun Huang; Huifen Jiang; Sunhong Hu; Yuehui Liu
Journal:  BMC Cancer       Date:  2010-04-18       Impact factor: 4.430

10.  Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer.

Authors:  H Wong; S Lau; T Yau; P Cheung; R J Epstein
Journal:  Br J Cancer       Date:  2010-04-27       Impact factor: 7.640

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