Title:
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The identification and validation of drug targets for
prostate cancer using integrated approaches
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Prostate cancer is a very complex disease, which we still do not fully understand. It is the
second most common cause of cancer- related death in men and therefore, it is very important
to investigate the mechanisms of prostate tumorigenesis and drug development. Membrane
proteins represent a valuable source of potential drug targets due to their intimate
involvement in a wide variety of disease states including but not limited to cancer. In our
study, we identified five drug targets, namely; EpCAM, TACSTD2, FAM3C, NCEHl and
TMEM109 abundantly present in the membrane fraction of prostate cancer cell lines using
proteomic approaches and validation of these proteins by other biological techniques. The
cumulative data from our study indicate that global levels of these five candidates either at
mRNA or protein levels are more present in prostate cancer cell lines and tissues than their
normal counterparts. We also found by ICC/IHC/IF that these five drug targets are subcellularly
localized in the cytoplasmic membrane region of prostate cancer cells and on the
basolateral surfaces of prostate tumour tissues. Taking into account the link between
T ACSTD2 and F AM3C to clinicopathological data of prostate tumour tissues stained and the
MTT survival assay carried out on prostate cancer cell lines, our data suggest that overexpression
ofTACSTD2 and FAM3C leads to poor prognosis in prostate cancer patients. We
also tried to study the relationship between our drug targets, CTCF and BORIS. Our
preliminary data shows a significant effect of CTCF and none of BORIS on our drug targets
in only DU145 cell lines. Suggesting these to be cell line specific and CTCF may play a role
in the transcriptional regulation of our target genes. Although, recently some of these
proteins have been widely explored, their function and the role they play in cancer
development still remain elusive.
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