| Abstract |
According to the World Health Organization (WHO) for 2020, prostate cancer is the most common malignancy diagnosed worldwide. The onset of the disease in up to 50% of patients appears to be due to the presence of ERG rearrangements, most notably the fusion of the 5’-untranslated region of the androgen-regulated TMPRSS2 gene close to the coding sequence of the transcriptional activator ERG, a member of the ETS transcriptional factors family. The transcriptional repressor ERF, which is a member of the ETS family, has been found mutated in 1% of prostate cancer cases, in the absence of other mutations in ETS genes. It is known through studies that ERF and ERG have common target genes. Therefore, it is possible that activation of ETS genes competes with the normal function of ERF. The present study aims at the morphological and histochemical study of the transcriptional repressor ERF loss in prostate cancer. For this purpose, transgenic animal models (Mus Musculus) have been generated with tissue-specific deletion of Erf and simultaneous tissue-specific deletion of the tumor suppressor gene Pten, which is considered a permissible genetic event for the development of the disease. Through histological examination of prostate sections was observed that the heterozygous deletion of Erf in older mice is not sufficient to trigger the full cancerous phenotype. Furthermore, the homozygous deletion of both Erf and Pten genes in young mice seems to result in a more aggressive phenotype of the disease which aggravates as the mice grow older. What is more, when the loss of Erf was combined with the heterozygous deletion of Pten, we observed prostate cancer aggravation in comparison with the mice that carried only heterozygous Pten deletion. However, all of the examined organs for metastatic regions had no evidence of lesions similar to the primary foci of lesion. Lastly, we isolated and studied prostate epithelial cells via immunofluorescence staining and quantitative Real Time PCR and we observed that the basal cells become extinct when the cells are cultured for long periods of time.
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Study of the transcriptional repressor ERF in prostate cancer
