Leukemia/Lymphoma Related Factor in Human Prostate Carcinoma
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Authors
Aggarwal, Himanshu
Issue Date
2008-05 , 2008-05
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Thesis
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en_US
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Abstract
Benign prostatic hyperplasia (BPH) and prostate cancer (PC) are critical health problems in elderly population with PC being the most common non-dermatologic malignancy in men. Although epidermal growth factor (EGF) plays a major role in the growth of normal prostate and in the initiation and progression of both BPH and PC, the exact underlying mechanisms of its role in pathogenesis of BPH and PC are unknown. Leukemia/lymphoma related factor (LRF)/ Pokemon (POK erythroid myeloid ontogenic factor) is a newly discovered transcription factor. It is a 72 kDa zinc-finger protein encoded by the ZBTB7A gene, which resides in the 19p13.3 locus. LRF/Pokemon belongs to POK family of transcriptional repressors that have been shown to play central role in human cell differentiation and development. Recently, high expression of LRF/Pokemon in human tumors, such as T and B cell lymphoma, nerve glioma, and non small cell lung carcinoma, has been found. However, the functional expression of LRF has not been examined in most common human solid tumors, including PC. The aim of this study was to investigate the expression of LRF/Pokemon in human BPH and PC tissues and to examine the effect of EGF on the expression of LRF/Pokemon in prostate cells.|The expression of LRF/Pokemon was examined in resected tissue specimens from the patients with BPH and prostate adenocarcinoma by immunohistochemistry and immunofluorescence using antibody against LRF/Pokemon. LRF/Pokemon was expressed in both BPH and PC glandular tissues with no/minimal expression in the surrounding tissue. Since LRF/Pokemon has been shown to be associated with proliferation, high expression of LRF/Pokemon suggests its potential role in the pathogenesis of both BPH and PC.|Normal prostate cells, RWPE-1, and prostate cancer cells, LNCaP (androgen sensitive) and PC3 (androgen-insensitive), were used to examine LRF/Pokemon expression by immunocytochemistry and immunofluorescence. The mean immunofluorescence intensity of LRF/Pokemon was significantly higher in PC3 and LNCaP cells than in RWPE-1 cells. Also, the expression of LRF/Pokemon was higher in PC3 cells than in the LNCaP cells. The semi-quantitative RT-PCR and Western blot analyses demonstrated the higher mRNA transcripts and protein expression, respectively, of LRF/Pokemon in cancer cells than in the normal prostate cells, with significantly greater expression of LRF/Pokemon in PC3 cells than in the LNCaP cells.|The treatment of the cells with various concentrations of EGF for 24 hrs increased both mRNA transcripts and protein expression of LRF/Pokemon in RWPE-1 and PC3 cells. The increase in the expression of LRF/Pokemon was quadratic with increasing doses of EGF. In EGF-treated LNCaP cells only mRNA transcript expression was increased while there was no significant increase in the protein expression of LRF/Pokemon.|Thus, the LRF/Pokemon is highly expressed in both BPH and PC glandular tissues. There is higher LRF/Pokemon expression in prostate cancer cells than in normal cells, with higher expression in androgen-insensitive (and thus more aggressive) prostate cancer cells than in androgen-sensitive cancer cells. This suggests a potential role of LRF/Pokemon in the initiation and progression of prostate cancer. Since EGF enhances the expression of LRF/Pokemon in both normal and prostate cancer cells, the increased expression of LRF/Pokemon in BPH and prostate cancer tissues could be due to increased activity of EGF-R in prostate glandular cells. Further studies are warranted to determine differential regulatory mechanisms of LRF/Pokemon in BPH and PC tissues.
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Creighton University
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Thesis-Aggarwal.pdf