Gene Expression Regulation, Neoplastic

Publication Title: 
Mechanisms of Ageing and Development

It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. In contrast, our results suggest that CR can act rapidly to begin life and health span extension, and that its rapid genomic effects are closely linked to its health effects. We found that CR begins to extend lifespan and reduce cancer as a cause of death within 8 weeks in older mice, apparently by reducing the rate of tumor growth.

Author(s): 
Spindler, Stephen R.
Publication Title: 
Mechanisms of Ageing and Development

An association between aging/longevity and cancer has long been suggested, yet the evolutionary and molecular links between these complicated traits remain elusive. Here, we analyze the relationship between longevity- and cancer-associated genes/proteins (LAGs/LAPs and CAGs/CAPs, respectively). Specifically, we address the following questions: (1) to what extent the CAGs and LAGs are evolutionary conserved and how they (or their orthologs) are related to each other in diverse species?

Author(s): 
Budovsky, Arie
Tacutu, Robi
Yanai, Hagai
Abramovich, Amir
Wolfson, Marina
Fraifeld, Vadim
Publication Title: 
FASEB journal: official publication of the Federation of American Societies for Experimental Biology

Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells.

Author(s): 
Li, Yuanyuan
Liu, Liang
Tollefsbol, Trygve O.
Publication Title: 
International Journal of Oncology

Telomeres are nucleoprotein structures at the ends of chromosomes that are composed of a repetitive G rich sequence and telomeric binding proteins. Telomeres prevent the degradation of chromosomal ends and protect against inappropriate recombination. Telomere attrition involves a tumor suppressor pathway that limits the replication of premalignant cells. The loss of telomeric DNA with each round of replication leads to growth arrest accompanied by senescence or apoptosis. Many tumor cells activate the telomerase gene to bypass senescence.

Author(s): 
Bojovic, Bojana
Crowe, David L.
Publication Title: 
Molecular Biology of the Cell

Forkhead box O (FOXO) transcription factors control diverse cellular functions, such as cell death, metabolism, and longevity. We analyzed FOXO3/FKHRL1 expression and subcellular localization in tumor sections of neuroblastoma patients and observed a correlation between nuclear FOXO3 and high caspase-8 expression. In neuroblastoma caspase-8 is frequently silenced by DNA methylation. Conditional FOXO3 activated caspase-8 gene expression but did not change the DNA-methylation pattern of regulatory sequences in the caspase-8 gene.

Author(s): 
Geiger, Kathrin
Hagenbuchner, Judith
Rupp, Martina
Fiegl, Heidi
Sergi, Consolato
Meister, Bernhard
Kiechl-Kohlendorfer, Ursula
M¸ller, Thomas
Ausserlechner, Michael J.
Obexer, Petra
Publication Title: 
PloS One

SIRT3, a mitochondrial sirtuin belonging to nicotinamide adenine nucleotide (NAD) dependent deacetylases, is implicated in metabolism, longevity and carcinogenesis. SIRT3 expression and its significance in hepatocellular carcinoma (HCC) remain largely unclear. In this study, we demonstrated that SIRT3 expression in HCC tissue was much lower than that in paracarcinoma tissue, at both mRNA and protein levels. The cutoff value for low SIRT3 expression in HCC was defined according to receiver operating characteristic curve (ROC) analysis.

Author(s): 
Zhang, Chris Zhiyi
Liu, Lili
Cai, Muyan
Pan, Yinghua
Fu, Jia
Cao, Yun
Yun, Jingping
Publication Title: 
Mechanisms of Ageing and Development

It is widely held that caloric restriction (CR) extends lifespan by preventing or reducing the age-related accumulation of irreversible molecular damage. In contrast, our results suggest that CR can act rapidly to begin life and health span extension, and that its rapid genomic effects are closely linked to its health effects. We found that CR begins to extend lifespan and reduce cancer as a cause of death within 8 weeks in older mice, apparently by reducing the rate of tumor growth.

Author(s): 
Spindler, Stephen R.
Publication Title: 
PloS One

Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from manipulating these same pathways might be offset by increased cancer risk on account of their propensity to boost cell survival. The Sir2/SIRT1 family of NAD(+)-dependent deacetylases is proposed to underlie the health benefits of calorie restriction (CR), a diet that broadly suppresses cancer in mammals.

Author(s): 
Firestein, Ron
Blander, Gil
Michan, Shaday
Oberdoerffer, Philipp
Ogino, Shuji
Campbell, Jennifer
Bhimavarapu, Anupama
Luikenhuis, Sandra
de Cabo, Rafael
Fuchs, Charles
Hahn, William C.
Guarente, Leonard P.
Sinclair, David A.
Publication Title: 
Journal of Neuro-Oncology

Regardless of their cell type of origin, all aggressive brain tumors, such as malignant gliomas and metastatic tumors produce brain edema, which is an important cause of patient morbidity and mortality. Caloric restriction (CR) has long been recognized as a natural therapy that improves health, promotes longevity, and significantly reduces both the incidence and growth of many tumor types. The aim of present work was to investigate the effect of CR on edema and survival in the mice implanted with U87 gliomas.

Author(s): 
Jiang, Yong-Sheng
Wang, Fu-Rong
Publication Title: 
Molecular and Cellular Biology

Telomerase canonically maintains telomeres, but recent reports have suggested that the core protein mammalian telomerase reverse transcriptase (TERT) component, together with the chromatin remodeling factor BRG1 and ?-catenin, may also bind to and promote expression of Wnt target genes. However, this proposed noncanonical role of TERT in Wnt signaling has been controversial. Here, we investigated the effects of human TERT (hTERT) on Wnt signaling in human breast cancer lines and HeLa cells.

Author(s): 
Listerman, Imke
Gazzaniga, Francesca S.
Blackburn, Elizabeth H.

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