A Prospective Role Of Specific Focal Adhesion Kinase Phosphorylation Sites As Prognostic Markers In Cancers Of Breast, Colon, Liver And Leukaemia

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dc.contributor.authorOmari, Saleh M S
dc.date.accessioned2018-06-28T02:24:27Z
dc.date.available2018-06-28T02:24:27Z
dc.date.issued2011-01
dc.description.abstractFocal Adhesion Kinase (FAK) is a 125 kDa non-receptor protein tyrosine kinase. FAK plays a pivotal role in the regulation of various cellular activities such as migration, adhesion, proliferation and growth. It has been reported that FAK has dual function as a scaffold and kinase protein. Analyses at the protein and cellular levels have demonstrated FAK overexpression and phosphorylation at specific residues in many tumours; however the data were mostly inconclusive and need further investigation. In this study, we set out to examine total FAK and phosphorylated FAK at various residues in breast, colon, liver cancer and leukemic cell lines in comparison to normal cell lines using Western blotting and immunofluorescent analyses. We propose that higher levels of phosphorylated FAK at Tyr 397 and Tyr 861 are highly required in the more invasive breast cancer. We also found that MDA-MB-231, breast cancer cells negatively expressing oestrogen receptor, exhibited higher FAK phosphorylation at Tyr 397 and Tyr 861. Higher expression of phospho-FAK Ser 910 was detected in the less invasive breast cancer cell lines, T-47D and MCF7, compared to the highly invasive MDA-MB-231. In regard to colon cancer, we found that moderately differentiated and less invasive colon cancer cell line, HT-29, expressed lower FAK level compared to the un-differentiated and more invasive colon cancer cell line, HCT 116. Phospho-FAK Tyr 397 was more expressed in HT-29 than in HCT 116. However, phosphorylation at Ser 910 was detected in normal and more differentiated cells, CCD-18Co and HT-29 respectively, but was undetectable in the more aggressive cells, HCT 116. These findings suggest that FAK phosphorylation at the two tyrosine residues, Tyr 397 and Tyr 861, may indicate a crucial requirement of these sites of phosphorylation in breast cancer invasiveness, since higher levels were observed in the more invasive cell lines. Contrary to breast cancer, FAK protein may be mainly required in the regulation of normal and differentiation colon cells, such as CCD-18Co and HT-29 respectively. Phosphorylation of FAK at Ser 910 appeared to have an inhibitory effect in breast cancer, since the less invasive cells, T-47D showed a higher level of phosphorylation at this residue whereas, both Tyr 397 and Tyr 861, were not phosphorylated. Based on our study, it is suggested that FAK phosphorylation at Ser 910 may play an important in retaining some of the characteristics of normal and differentiated phenotypes.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/5809
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectA prospective role of specific focal adhesion kinase phosphorylation sitesen_US
dc.subjectas prognostic markers in cancers of breast, colon, liver and leukaemiaen_US
dc.titleA Prospective Role Of Specific Focal Adhesion Kinase Phosphorylation Sites As Prognostic Markers In Cancers Of Breast, Colon, Liver And Leukaemiaen_US
dc.typeThesisen_US
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