B217: Investigating the possible role of FABP9 in malignant progression of prostate cancer
1University of Liverpool, Liverpool, UK
Our previous studies showed that FABP5 plays an important role in promoting malignant progression of prostate cancer cells. Thus FABP5 was proved to be prognostic marker and a possible novel treatment target for advanced prostate cancer. Now that FABP5 has been shown to be an important molecule in malignant progression of prostate cancer, what about other members of the FABP family, do they also play important roles as FABP5? This study is aimed to establish or eliminate the possible roles of other FABPs in development and spread of prostate cancer. We first studied whether the increased expression of FABP9 was associated with increasing malignancy of prostate cancer cells and tissues, then we explored whether FABP9 played a promoting role in prostate cancer.
Expression levels of FABP family members in benign and malignant prostate cell lines were detected by qPCR at mRNA level and by Western blotting at protein level. The expression of FABP9 in BPH and in prostate carcinoma tissues was detected by immunohistochemistry staining. RNAi technique was used to suppress the expression of FABP9 in PC3-M cells and to establish transfectant clones expressing reduced level of FABP9. The possible promoting role of FABP9 in tumorigenicity of the cancer cells will be studied by investigating whether suppressed FABP9 can inhibit tumourigenicity via testing the RNAi transfectants both in vitro and in vivo.
Our data showed that levels of FABP1, 2, 3,4,6,7 and 8 expressed in prostate epithelial cells were not substantially changed as the changing of the malignancy of the cells, but the expression of FABP9 expression was different. At mRNA level, more FABP9 mRNA was transcribed in malignant cells than in the benign cells. While no detectable protein was observed in the benign cell line PNT2, low and moderately malignant cell lines LNCaP, 22RV1; the level of FABP9 expression was remarkably increased in most highly malignant cell lines. Immunohistochemical analysis showed that the staining intensity of FABP9 was significantly higher in carcinoma than in BPH. Increase cytoplasmic staining for FABP9 was correlated with the increasing malignancy indicated by Gleason scores. Moreover, cytoplasmic staining for FABP9 was significantly associated with patient survival time and androgen receptor (AR) level. The direct effect of suppressing FABP9 in tumorigenicity is currently being tested both in vitro and in vivo.
Our preliminary results showed that FABP9 is over expressed in both prostate cancer cell lines and in carcinomas tissues. Further studies are needed to characterise the functional activity of FABP9 in prostate cancer cells by subsequent bioassays in vitro and in vivo.