Telomerase and Telomeres in Endometrial Cancer

Abstract

Telomeres at the termini of human chromosomes are shortened with each round of cell division due to the “end replication problem” as well as oxidative stress. During carcinogenesis, cells acquire or retain mechanisms to maintain telomeres to avoid initiation of cellular senescence or apoptosis and halting cell division by critically short telomeres. The unique reverse transcriptase enzyme complex, telomerase, catalyzes the maintenance of telomeres but most human somatic cells do not have sufficient telomerase activity to prevent telomere shortening. Tissues with high and prolonged replicative potential demonstrate adequate cellular telomerase activity to prevent telomere erosion, and high telomerase activity appears to be a critical feature of most (80–90%) epithelial cancers, including endometrial cancer. Endometrial cancers regress in response to progesterone which is frequently used to treat advanced endometrial cancer. Endometrial telomerase is inhibited by progestogens and deciphering telomere and telomerase biology in endometrial cancer is therefore important, as targeting telomerase (a downstream target of progestogens) in endometrial cancer may provide novel and more effective therapeutic avenues. This review aims to examine the available evidence for the role and importance of telomere and telomerase biology in endometrial cancer.

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

“…POT1 binds directly to the single stranded 3′ end of the telomere and forms a heterodimer with TPP1. TERF1 and TERF2 bind to the double-stranded telomeric sequence [ 11 ]. (Created with ).…”

“…In addition to this, they limit cellular proliferation by shortening in length with each round of DNA replication until they reach a critical length, which induces permanent cell-cycle arrest [ 8 , 9 , 10 ]. Telomere length can be regulated by one of two mechanisms: the well-established telomerase dependent pathway or by the more recently described alternative lengthening of telomeres (ALT) pathway [ 11 ]. Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA sequences using an RNA template ( Figure 1 ) [ 7 ].…”

“…Telomerase is a reverse transcriptase enzyme that synthesizes telomeric DNA sequences using an RNA template ( Figure 1 ) [ 7 ]. In contrast, the ALT pathway utilises homologous recombination repair to synthesise new telomeric DNA [ 11 ].…”

Human Uterine Biopsy: Research Value and Common Pitfalls

“…The uterus is a hormonally responsive organ, and it is the principal target for many hormones including ovarian sex steroids [1,2]. The main discerning feature of the human uterus is menstruation, which is a unique process, and is limited to humans and upper-order primates; thus, this particular aspect of human uterine biology cannot easily be modelled in common laboratory animal models (e.g., murine or rodent models) [3]. Therefore, patient-derived uterine biopsies are invaluable to further our current understanding of human uterine biology.…”

“…Furthermore, full-thickness biopsies taken from this thin endometrium in a hysterectomy sample (and even possibly from a curettage) invariably contain the underlying myometrium; thus, the studies examining the expression of endometrial-specific genes may be affected by the myometrial expression levels that are included in the whole biopsy. In endometrial cancer research, it is challenging, and not usually possible, to obtain a full-thickness uterine biopsy for snap freezing or RNA studies, as the specimen must be initially preserved whole for pathologists' scrutiny and staging purposes [3]. Hence, curettes or pipelle biopsies are the only available sampling methods for most studies.…”