Expression of FABP6 and FABP9 in prostate cancer and their relationship to malignant progression



Al Fayi, MS
(2017) Expression of FABP6 and FABP9 in prostate cancer and their relationship to malignant progression. PhD thesis, University of Liverpool.

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Abstract

The increased expression of fatty acid binding protein 4 (FABP4) and 5 (FABP5) play a crucial role in promoting tumorigenicity and metastasis of prostate cancer. FABP4 was suggested to be a therapeutic target for metastasis of prostate cancer. FABP5 was also proven to be a prognostic marker and potential treatment target. In contrast to numerous studies conducted to investigate the crucial role of FABP4 and FABP5 in prostate cancer, investigations on the possible involvement of other FABPs in the malignant progression of prostate cancer are rare. To find out whether any other FABP family proteins can also be used as diagnostic or prognostic markers for prostate cancer as FABP5, we measured the mRNA levels of 10 FABPs in benign and malignant prostate cell lines. Results showed that FABP4, FABP5, FABP6, FABP9 and FABP12 exhibited clearly higher levels in all tested malignant cell lines compared to their levels in the benign PNT-2 cells. Although, FABP4 and FABP5 have been associated with human prostate cancer as revealed in studies of our group and other groups, the finding of potential roles of FABP6, FABP9 and FABP12 have not been addressed. FABP12 is the most recently discovered member and no antibody was available for this candidate, thus FABP12 will be studied in a separate project of the group. Thereafter we assessed the expression status of FABP6 and FABP9 in both human prostate cell lines and tissues at the protein level. FABP6 protein was overexpressed only in 1 of the 5 malignant cell lines and its immunohistological staining intensities were not significantly different between the benign and the malignant prostate tissues. In contrast, FABP9 protein was highly expressed in highly malignant cell lines PC-3 and PC3-M, but its level in the benign PNT-2 and other malignant cell lines was not detectable. When analysed in an archival set of human prostate tissues, immunohistological staining intensity for FABP9 was significantly higher in carcinomas than in benign cases and the increase in FABP9 was significantly correlated with reduced patient survival times. Moreover, the increased level of staining for FABP9 was significantly associated with the increased joint Gleason scores (GS) and androgen receptor index (AR). Suppression of FABP9 expression in highly malignant PC3-M cells inhibited their invasive potential, but did not affect their growth rate, anchorage-independent growth and migration rate. Our results suggest that FABP9 is a valuable prognostic marker to predict the outcomes of prostate cancer patients, perhaps by playing an important role in prostate cancer cell invasion.

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 21 Aug 2017 06:24
Last Modified: 11 Sep 2021 07:10
DOI: 10.17638/03006298
Supervisors:
  • Prof Youqiang Ke,
  • Dr Syed Hussain,
URI: https://livrepository.liverpool.ac.uk/id/eprint/3006298