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Investigation of the differentially expressed C-FABP & FABP-pm in human prostate tissues and cell lines: histopathological and molecular biology study

Lookup NU author(s): Dr Imad Malki

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Abstract

nontobacco related cancers of man in the developed world. Our understanding of the molecular pathology of prostate cancer is currently very limited. At present, clinical therapy focuses on androgen blockage by physical or pharmaceutical castration. Previous work in our pathology laboratory has led to the identification of several genes whose elevated expression may contribute to the malignant progression of the prostate cancer cells. Tow of these genes are that coding for human cutaneous fatty acid binding protein (C-FABP) and membrane associated fatty acid binding protein (FABP-pm). The work described in this research is aimed to study further the possible role of C-FABP and FABP-pm on prostate cancer tumourigencity, to investigate whether these two FABPs modulate the malignant progression of prostate cancer cells in a coordinated manner and to explore the therapeutic possibilities by manipulating their expressions in prostate cancer cells. Materials and Methods: Immunhistochemical staining for human prostate tissues comprised an archival set with follow-up data held within the diagnostic archive in the Department of Pathology, University of Liverpool, UK. Tissues were taken from 73 prostate adenocarcinoma patients with an average age of 73 years and from 33 benign prostatic hyperplasia (BPH) patients with an average age of 67.5 years who were treated by trans-urethral resection of prostate (TURP) in the Royal Liverpool University Hospital during the 8-years of 1995–2003. The 7 normal prostate tissues were taken from road accident victims with an average age of 48 years who did not have a history of prostatic disease. This study was approved by Liverpool Local Science Ethics Committee in accordance with the Medical Research Council guidelines. The PC3, DU145, PC3M, PC3M3, 22RV1, LNCaP-WT and LNCaP prostatic cancer cell lines with the non malignant cell line PNT2 were used for Cell Culture and Western blotting to analyse the cellular proteins. All cell lines were obtained from the storage of the Department of Pathology, University of Liverpool. Results: Western blot results showed that the expression of C-FABP was significantly higher in androgen independent cell lines than that in androgen dependent cell lines whereas the expression of FABP-pm was significantly higher in androgen dependent cell lines than that observed in androgen independent cell lines. These results showed that C-FABP and FABP-pm express in opposite manner in prostate cancer progression. Immunhistochemical staining of an archival set of prostate cancer tissues partially supported this relationship between these two genes as levels of both nuclear and cytoplasmic C-FABP expression in carcinoma tissues were significantly higher than those in normal and PBH tissues whilst the FABP-pm expression in normal and BPH tissues were significantly higher than those in carcinoma tissues. Conclusion: These results together seemed to suggest that the C-FABP and FABP-pm express in opposite manner in prostate cancer progression. These findings indicated that increased expression of C-FABP or decreased expression of FABP-pm maybe a valuable prognostic factor predicting the outcome in prostate cancer patients, and it may also prove to be an important target for designing effective strategies to treat the disease.


Publication metadata

Author(s): Malki MI, Forootan S, Foster CS, Ke Y

Publication type: Article

Publication status: Published

Journal: European Journal of Cancer Supplements

Year: 2010

Volume: 8

Issue: 5

Pages: 198

Print publication date: 29/06/2010

ISSN (print): 1359-6349

Publisher: European Journal of Cancer

URL: http://dx.doi.org/10.1016/S1359-6349(10)71584-6

DOI: 10.1016/S1359-6349(10)71584-6


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