Microgravity Affects Thyroid Cancer Cells during the TEXUS-53 Mission Stronger than Hypergravity
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Authors: Kopp, Sascha; Krueger, Marcus; Bauer, Johann; Wehland, Markus; Corydon, Thomas J.; Sahana, Jayashree; Nassef, Mohamed Zakaria; Melnik, Daniela; Bauer, Thomas J.; Schulz, Herbert; Schuette, Andreas; Schmitz, Burkhard; Oltmann, Hergen; Feldmann, Stefan; Infanger, Manfred; Grimm, Daniela
Abstract
Thyroid cancer is the most abundant tumor of the endocrine organs. Poorly differentiated thyroid cancer is still difficult to treat. Human cells exposed to long-term real (r-) and simulated (s-) microgravity (mu g) revealed morphological alterations and changes in the expression profile of genes involved in several biological processes. The objective of this study was to examine the effects of short-term mu g on poorly differentiated follicular thyroid cancer cells (FTC-133 cell line) resulting from 6 min of exposure to mu g on a sounding rocket flight. As sounding rocket flights consist of several flight phases with different acceleration forces, rigorous control experiments are mandatory. Hypergravity (hyper-g) experiments were performed at 18g on a centrifuge in simulation of the rocket launch and s-mu g was simulated by a random positioning machine (RPM). qPCR analyses of selected genes revealed no remarkable expression changes in controls as well as in hyper-g samples taken at the end of the first minute of launch. Using a centrifuge initiating 18g for 1 min, however, presented moderate gene expression changes, which were significant for COL1A1, VCL, CFL1, PTK2, IL6,CXCL8 and MMP14. We also identified a network of mutual interactions of the investigated genes and proteins by employing in-silico analyses. Lastly, mu g-samples indicated that microgravity is a stronger regulator of gene expression than hyper-g.
Effect of TERT and ATM on gene expression profiles in human fibroblasts
GENES CHROMOSOMES & CANCER
Authors: Baross, A; Schertzer, M; Zuyderduyn, SD; Jones, SJM; Marra, MA; Lansdorp, PM
Abstract
Telomeres protect chromosomes from degradation, end-to-end fusion, and illegitimate recombination. Loss of telomeres may lead to cell death or senescence or may cause genomic instability, leading to tumor formation. Expression of human telomerase reverse transcriptase (TERT) in human fibroblast cells elongates their telomeres and extends their lifespan. Ataxia telangiectasia mutated (ATM) deficiency in A-T human fibroblasts results in accelerated telomere shortening, abnormal cell-cycle response to DNA damage, and early senescence. Gene expression profiling was performed by serial analysis of gene expression (SAGE) on BJ normal human skin fibroblasts, A-T cells, and BJ and A-T cells transduced with TERT cDNA and expressing telomerase activity. In the four SAGE libraries, 36,921 unique SAGE tags were detected. Pairwise comparisons between the,libraries showed differential expression levels of 1%-8% of the tags. Transcripts affected by both TERT and ATM were identified according to expression patterns, making them good candidates for further studies of pathways affected by both TERT and ATM. These include MT2A, P4HB, LGALS1, CFL1, LDHA, S100A10, E1F3S8, RANBP9, and SEC63. These genes are involved in apoptosis or processes related to cell growth, and most have been found to be deregulated in cancer. Our results have provided further insight into the roles of TERT and ATM by identifying genes likely to be involved in their function. (C) 2004 Wiley-Liss, Inc.