HTERT-driven immortalization of human sertoli cells down-regulates P۵۳ expression

Telomere is a structure composed of DNA and proteins made by the telomerase enzyme. This enzyme is present in high levels in cancer, stem and embryonic cells, but its expression is reduced in normal somatic cells. Transcription factor P۵۳ is a tumor suppressor expressed in more than ۵۰% of cancer cells. In recent years, the correlation between P۵۳ expression and HTERT has been recognized and in this study this relationship was clearly observed. Telomere sequence shortens during the cell cycle and by reaching a critical level the threshold leads to cell cycle arrest. Telomerase has two main subunits, HTERT and HTERC, the former of which is the catalytic subunit and the latter is the template strand. Telomerase has been considered as an anti-apoptotic factor through inhibiting apoptotic signals and circumvent aging. Therefore, inhibition of HTERT is considered as a tumor suppressor. The relationship between p۵۳ and HTERT is both direct and indirect. Direct binding of p۵۳ to sub-telomeric area will alter the transcription and chromatin conformation. HTERT promoter has binding sites for c-myc, SP۱, and P۵۳. In this study; sertoli cells - which naturally exhibit degree of resemblance to the metabolic state of cancer cells - were transduced and immortalized by a lentivirus containing HTERT. For both non-immortal and immortal sertoli cells, RT-PCR was performed with two pairs of HTERT and P۵۳ primers, which showed high expression of HTERT in immortal Sertoli cells and decreased expression of P۵۳ in them. Previous studies such as p۵۳ knock-down have shown an increase in HTERT expression. In some studies, overexpression of HTERT led to decreased expression of p۵۳. In this study, an increased HTERT expression ectopically, reduced P۵۳ expression significantly. Although more studies are needed in this area, such results are a bright horizon for future HTERT-based anticancer therapies.

کلیدواژه ها:

Apoptosis ، Cancer ، Immortality ، RT-PCR