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Simple Summary The expression of the catalytic subunit of the human telomerase reverse transcriptase subunit (hTERT) is hormonally controlled. Androgen treatment suppresses the hTERT expression at a transcriptional level in prostate cancer cells. Here, we identified the responsive promoter element that mediates the androgen receptor induced transrepression of hTERT. The negative androgen response element (nARE) is identified as 62 bp located in the core promoter of hTERT. Chromatin immunoprecipitations indicate an androgen-dependent recruitment of the androgen receptor (AR) ING1 and ING2 to the hTERT promoter. Interestingly, the androgen-induced transrepression is mediated by the class II tumor suppressors inhibitor of growth 1 and 2, namely ING1 and ING2, respectively. Abstract The human telomerase is a key factor during tumorigenesis in prostate cancer (PCa). The androgen receptor (AR) is a key drug target controlling PCa growth and regulates hTERT expression, but is described to either inhibit or to activate. Here, we reveal that androgens repress and activate hTERT expression in a concentration-dependent manner. Physiological low androgen levels activate, while, notably, supraphysiological androgen levels (SAL), used in bipolar androgen therapy (BAT), repress hTERT expression. We confirmed the SAL-mediated gene repression of hTERT in PCa cell lines, native human PCa samples derived from patients treated ex vivo, as well as in cancer spheroids derived from androgen-dependent or castration resistant PCa (CRPC) cells. Interestingly, chromatin immuno-precipitation (ChIP) combined with functional assays revealed a positive (pARE) and a negative androgen response element (nARE). The nARE was narrowed down to 63 bp in the hTERT core promoter region. AR and tumor suppressors, inhibitor of growth 1 and 2 (ING1 and ING2, respectively), are androgen-dependently recruited. Mechanistically, knockdown indicates that ING1 and ING2 mediate AR-regulated transrepression. Thus, our data suggest an oppositional, biphasic function of AR to control the hTERT expression, while the inhibition of hTERT by androgens is mediated by the AR co-repressors ING1 and ING2.

Aim and Background: Due to the relatively high prevalence of binocular vision anomalies, a regular examination including tests for assessment and determination of these anomalies is necessary. The aim of this study was to assess the relationship between near point of convergence (NPC) and near binocular vision symptoms and finding of an NPC cutoff point for symptoms in university students. Materials and Methods: In this cross-sectional study, 124 students of different majors of Zahedan University of Medical Sciences were randomly selected. If they met the inclusion criteria, they were divided into two groups (symptomatic and asymptomatic) according to the convergence insufficiency symptom survey questionnaire. For NPC measurement, a small isolated letter "E" of approximately 20/30 size on a metal rod was used. After data collection, data were analyzed in SPSS.17 software (SPSS for Windows, SPSS Inc., Chicago, IL) using descriptive and analytical statistics, including Mann-Whitney U test and receiver operating characteristic (ROC) curve. Results: The mean NPC findings in the symptomatic and asymptomatic groups were 11.7 ± 5.0 and 8.4 ± 3.4 cm, respectively, with a significant difference between the two groups (P < 0.001). The ROC curve suggests an NPC cutoff point of 9.5 cm for the presence of symptoms with the testing procedures used in this study. Conclusion : The determination of NPC is helpful in the differentiation of symptomatic from asymptomatic subjects.