Journal of Cancer Therapy, 2012, 3, 7-19 doi:10.4236/jct.2012.31002 Published Online February 2012 (http://www.SciRP.org/journal/jct) 7 Studies on Focal Adhesion Kinase in Human Breast Cancer Tissue Kirat Kumar Ganguly 1 , Triparna Sen 1 , Syamsundar Mandal 2 , Jaydip Biswas 3 , Amitava Chatterjee 1* 1 Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India; 2 Department of Epi- demiology & Biostatistics, Chittaranjan National Cancer Institute, Kolkata, India; 3 Department of Surgical Oncology, Chittaranjan National Cancer Institute, Kolkata, India. Email: * amitava_chatter@yahoo.co.in Received November 26 th , 2011; revised December 25 th , 2011; accepted January 14 th , 2012 ABSTRACT Aim: To study Expression and Phosphorylation status of Focal Adhesion Kinase (FAK) in Human Breast Cancer tissue. To study the relation of FAK with standard clinicopathological parameters of Human Breast Cancer. Methods: Tissue collection, Protein extraction, RNA isolation, Western Blot, Immunohistochemistry, RT-PCR, ELISA, Statistical analy- sis. Results: All the four techniques showed upregulated expression, phosphorylation (Tyr-397) and processing of FAK in human breast cancer tissue compared to the adjacent non-tumor tissue of the same patient. Upregulation of FAK was found to be increased parallely with the advancement of cancer. Localisation of FAK was found to be membrano-cyto- plasmic. FAK is upregulated both in protein and mRNA level. Expression and phosphorylation of FAK is increased specifically in the tumor regions compared to the surrounding non-tumor region. Upregulation of FAK was frequently found in ER-positive and PR-positive but Her2/neu-negative breast cancer cases. Conclusion: FAK has crucial role in development and progression of human breast cancer. FAK may be considered as an indicator of human breast cancer progression. FAK processing may be considered as an indicator of invasive potential of breast cancer. FAK may be considered as a clinical indicator of human breast cancer development and progression. Keywords: FAK; Human Breast Cancer 1. Introduction Focal adhesion kinase (FAK) is a 125 kD nonreceptor protein tyrosine kinase that localizes at the cellular adhe- sion points. It is a crucial mediator of signaling events between cells and cell surrounding extracellular matrix (ECM). FAK is ubiquitously expressed throughout de- velopment and well detectable in physiological adult tissues. FAK is mainly involved in integrin-signaling pa- thways, by binding with the β1 subunit of Integrin [1-4]. Interaction of FAK with a number of signaling molecules situates it at a junction of signal transduction network and regulates cell migration [5-9] and apoptosis [10-17], cell proliferation [18-22] etc. In response to clustering of integrins due to ligand interaction, FAK is get activated by an autophosphorylation at Tyrosine-397 [23]. FAK imparts its activity both as a Kinase enzyme and an adaptor molecule [24,25]. During tumor development and cancer progression, it is thought that FAK have a double purpose both in promoting tumor cell adhesion during cell migration and in maintaining cell survival to inhibit apoptosis as a tumor develops anchorage-inde- pendent growth properties. The connection of FAK with breast cancer was first proposed by analyses with tissue homogenates showing that both FAK protein and mRNA were appreciably upregulated in invasive and metastatic breast tumor sam- ples in comparison to matched normal tissues [26]. Latter on several studies showed crucial role of FAK in breast cancer. Importance of FAK in breast cancer biology was confirmed in experiments by depletion of FAK with an- tisense oligonucleotides causing an inhibition of cell mi- gration, invasion and proliferation as well as induction of apoptosis [27-33]. Moreover, studies with xenograft mo- dels indicated role of FAK in subcutaneous tumor forma- tion, in promotion of mammary tumor growth, in early phase of metastasis, in facilitation of angiogenic signal in mammary tumors etc [30,34,35]. Studies by different groups with human tissue speci- mens have demonstrated specific up-regulation of FAK expression in high-grade sarcomas [36] and tumors from breast, colon, thyroid, ovarian, cervix, head-neck and esophagus [37]. Studies by several groups confirmed a pivotal role of FAK in tumorigenesis and metastasis [38]. These observations indicate towards the relevance FAK * Corresponding author. Copyright © 2012 SciRes. JCT