Tumour specific regulation of telomerase RNA gene expression visualized by in situ hybridization

Maintenance of telomere structure by the ribonucleoprotein enzyme telomerase is considered central to the development of most human cancers, However, regulatory mechanisms governing telomerase expression during oncogenesis are largely unknown. We address potential tumour-specific regulation of telomerase RNA gene expression by RNA in situ hybridization to over 300 tumour samples of germ cell and epithelial origin, Twenty-six per cent of non-small cell lung cancers (NSCLC), expressed detectable levels of the telomerase RNA gene (hTR), and interestingly expression was almost confined to squamous carcinomas (41%), being rare in pulmonary adenocarcinomas and large-cell anaplastic carcinomas (P=0.006), Low frequency hTR expression was also associated with adenocarcinoma of the breast (13%), and ovary (17%), In comparison, hTR expression was detected in 43% of cervical cancers with no significant differences in frequency between squamous-cell carcinoma and adenocarcinoma or in transitions between intraepithelial neoplasia and invasive carcinoma, In contrast to the common epithelial cancers, the malignant cells in 73% of testicular germ-cell tumours (seminomas and teratomas), expressed hTR consistent with hTR expression in normal testicular germ cells, Differentiated tissues within ovarian germ cell tumours and in testicular teratomas lacked detectable hTR expression, These studies show that different tumour types have distinct patterns of hTR expression, which has implications for our understanding of mechanisms regulating telomerase activity and for targeting the telomerase RNA component as an anti-cancer therapy

Is small cell lung cancer the perfect target for anti- telomerase treatment?

Small cell lung cancer (SCLC) is common in men and women, has<SUP> </SUP>a very poor prognosis, and is therefore a major cause of premature<SUP> </SUP>mortality. As such, any prospects for improved therapy are of<SUP> </SUP>great significance. The promise of telomerase as a therapeutic<SUP> </SUP>target is now close to realization with extremely encouraging<SUP> </SUP>preclinical studies aimed at the RNA component (hTR) of telomerase.<SUP> </SUP>The rational integration of telomerase therapeutics into clinical<SUP> </SUP>trials will therefore require tumours to be well characterized<SUP> </SUP>for hTR expression. Despite the large number of cancer types<SUP> </SUP>now characterized for telomerase or telomerase component gene<SUP> </SUP>expression, only a handful of SCLC samples have been analysed.<SUP> </SUP>Given the major clinical problem with treating SCLC, we specifically<SUP> </SUP>set out to address the issue of hTR expression in neuroendocrine<SUP> </SUP>tumours. Our study covers 91 pulmonary neuroendocrine tumours<SUP> </SUP>(62 SCLC and 29 carcinoid tumours). We present data to show<SUP> </SUP>that upregulation of the RNA component of telomerase occurs<SUP> </SUP>in 98% of human SCLCs. Interestingly, the less aggressive carcinoid<SUP> </SUP>tumours of the lung had a significantly lower frequency of hTR<SUP> </SUP>expression (<I>P</I> < 0.01). Importantly, we compare hTR expression<SUP> </SUP>in this series to the well characterized biological targets<SUP> </SUP>p53 and BCL2, and show hTR to be expressed more frequently.<SUP> </SUP>Therapies directed at the RNA component of human telomerase<SUP> </SUP>are in active development and these data show SCLC to be a prime<SUP> </SUP>target for such therapies

Visceral adipose tissue and cardiometabolic risk factors in young Hispanic and non-Hispanic girls

Background: Risk factors for cardiometabolic diseases (e.g., type 2 diabetes, cardiovascular disease) can begin developing in childhood. Elevated body mass index (BMI) is associated with greater likelihood of developing such diseases; however, this relationship varies by race and ethnicity. Notably, Hispanics tend to have high rates of obesity and are disproportionately affected by type 2 diabetes. We aimed to determine if visceral adiposes tissue (VAT) is associated with cardiometabolic risk factors (i.e., triglycerides, cholesterol, insulin resistance, C-reactive protein, and blood pressure), independent of BMI percentile, in a sample of primarily Hispanic adolescent girls. Methods and results: A total of 337 girls (73% Hispanic) took part in the cross-sectional study. Hispanic girls generally had greater BMI percentile, VAT, and cardiometabolic risk factors compared to non-Hispanic girls. Multiple linear regression was used to assess the relationships between Dual-energy X-ray Absorptiometry (DXA)-derived VAT and cardiometabolic outcomes, controlling for BMI percentile (<85th percentile or ≥85th percentile), age, ethnicity (Hispanic/non-Hispanic), and Tanner stage. Significant interactions between VAT and BMI percentile were identified for almost all cardiometabolic outcomes. Upon stratification, the association between VAT and cardiometabolic outcomes was strongest in girls ≥85th BMI percentile, as compared to girls <85th percentile. However, VAT was only significantly associated with higher triglycerides (girls ≥85th percentile) and higher insulin resistance (both BMI percentiles) after stratification. Conclusion: VAT was associated with increased triglycerides and insulin resistance in girls with overweight or obesity. These findings warrant further investigation between VAT and cardiometabolic health in Hispanic adolescents who tend to accumulate more adipose tissue during adolescence. Copyright © 2022 Bland, Kindler, Blew, Morrill, Roe and Going.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]