Androgens stimulate telomerase expression, activity and phosphorylation in ovarian adenocarcinoma cells
ABSTRACT Androgens have been implicated in increasing ovarian cancer risk. Most ovarian cancer cells have high telomerase activity which is effective in inducing ovarian carcinogenesis. The purpose of this study was to investigate the effects of testosterone and androstenedione on the viability of an ovarian adenocarcinoma cell line, the activity and expression of telomerase, and the phosphorylation status of its catalytic subunit in these cells. Results showed that androgens significantly increased the viability of ovarian cancer cells and that these hormones induced the expression, activity and phosphorylation of telomerase. This upregulation was blocked by phosphatidylinositol 3-kinase pathway inhibitors. These findings might have implications for understanding the role of androgens in ovarian carcinogenesis.
SourceAvailable from: Cristiana Libardi Miranda-Furtado[Show abstract] [Hide abstract]
ABSTRACT: To analyze whether leukocyte telomere length (LTL) is impaired in women with polycystic ovary syndrome (PCOS). Case-control study. Hospital. A total of 274 women, including 150 patients with PCOS and 124 controls. None. Body mass index (BMI), waist circumference, systemic arterial pressure, lipid profile, E2, LH, T, androstenedione, PRL, TSH, sex hormone-binding globulin, C-reactive protein (CRP), homocysteine, free androgen index, and the homeostatic model of insulin sensitivity (HOMA-IR) index were analyzed. The LTL evaluation was measured by quantitative polymerase chain reaction. The PCOS group had higher values for weight, BMI, waist circumference, systolic arterial pressure, triglycerides, LH, T, insulin, CRP, free androgen index, and HOMA-IR compared with the control group. Sex hormone-binding globulin and E2 levels were lower in the PCOS group than in the control group. The LTL did not differ between groups. Age, BMI, and HOMA-IR had no significant effect on LTL. The inflammatory biomarkers CRP and homocysteine were negatively correlated with LTL in patients with PCOS. Our results showed no differences in LTL between patients with PCOS and controls, but CRP and homocysteine biomarkers negatively correlated with LTL in the PCOS group. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.Fertility and Sterility 11/2014; DOI:10.1016/j.fertnstert.2014.10.035 · 4.30 Impact Factor
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ABSTRACT: Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and dyskeratosis congenita are inherited syndromes characterized by marrow failure, congenital anomalies, and cancer predisposition. Genetic and molecular studies have uncovered distinct abnormalities in ribosome biogenesis underlying each of these three disorders. How defects in ribosomes, the essential organelles required for protein biosythesis in all cells, cause tissue-specific abnormalities in human disease remains a question of fundamental scientific and medical importance. Here we review the overlapping and distinct clinical features of these three syndromes and discuss current knowledge regarding the ribosomal pathways disrupted in each of these disorders. We also explore the increasing complexity of ribosome biology and how this informs our understanding of developmental biology and human disease.Blood 09/2014; 124(18). DOI:10.1182/blood-2014-04-526301 · 9.78 Impact Factor
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ABSTRACT: Human degenerative disc disease (DDD) is characterized by progressive loss of human nucleus pulposus (HNP) cells and extracellular matrix, in which the massive deposition are secreted by HNP cells. Cell therapy to supplement HNP cells to degenerated discs has been thought to be a promising strategy to treat DDD. However, obtaining a large quality of fully functional HNP cells has been severely hampered by limited proliferation capacity of HNP cells in vitro. Previous studies have used lipofectamine or recombinant adeno-associated viral (rAAV) vectors to deliver human telomerase reverse transcriptase (hTERT) into ovine or HNP cells to prolong the activity of nucleus pulposus cells with limited success. Here we developed a lentiviral vector bearing both hTERT and a gene encoding green fluorescence protein (L-hTERT/EGFP). This vector efficiently mediated both hTERT and EGFP into freshly isolated HNP cells. The expressions of both transgenes in L-hTERT/EGFP transduced HNP cells were detected up to day 210 post viral infection, which was twice as long as rAAV vector did. Furthermore, we observed restored telomerase activity, maintained telomere length, delayed cell senescence, and increased cell proliferation rate in those L-hTERT/EGFP transduced HNP cells. Our study suggests that lentiviral vector might be a useful gene delivery vehicle for HNP cell therapy to treat DDD. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res XX:XXX-XXX, 2013.Journal of Orthopaedic Research 01/2014; 32(1). DOI:10.1002/jor.22474 · 2.88 Impact Factor