TITLE

Novel functional view of the crocidolite asbestos-treated A549 human lung epithelial transcriptome reveals an intricate network of pathways with opposing functions

AUTHOR(S)
Hevel, Joan M.; Olson-Buelow, Laura C.; Ganesan, Balasubramanian; Stevens, John R.; Hardman, Jared P.; Aust, Ann E.
PUB. DATE
January 2008
SOURCE
BMC Genomics;2008, Vol. 9, Special section p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Although exposure to asbestos is now regulated, patients continue to be diagnosed with mesothelioma, asbestosis, fibrosis and lung carcinoma because of the long latent period between exposure and clinical disease. Asbestosis is observed in approximately 200,000 patients annually and asbestos-related deaths are estimated at 4,000 annually. Although advances have been made using single gene/gene product or pathway studies, the complexity of the response to asbestos and the many unanswered questions suggested the need for a systems biology approach. The objective of this study was to generate a comprehensive view of the transcriptional changes induced by crocidolite asbestos in A549 human lung epithelial cells. Results: A statistically robust, comprehensive data set documenting the crocidolite-induced changes in the A549 transcriptome was collected. A systems biology approach involving global observations from gene ontological analyses coupled with functional network analyses was used to explore the effects of crocidolite in the context of known molecular interactions. The analyses uniquely document a transcriptome with function-based networks in cell death, cancer, cell cycle, cellular growth, proliferation, and gene expression. These functional modules show signs of a complex interplay between signaling pathways consisting of both novel and previously described asbestos-related genes/gene products. These networks allowed for the identification of novel, putative crocidolite-related genes, leading to several new hypotheses regarding genes that are important for the asbestos response. The global analysis revealed a transcriptome that bears signatures of both apoptosis/cell death and cell survival/proliferation. Conclusion: Our analyses demonstrate the power of combining a statistically robust, comprehensive dataset and a functional network genomics approach to 1) identify and explore relationships between genes of known importance 2) identify novel candidate genes, and 3) observe the complex interplay between genes/gene products that function in seemingly different processes. This study represents the first function-based global approach toward understanding the response of human lung epithelial cells to the carcinogen crocidolite. Importantly, our investigation paints a much broader landscape for the crocidolite response than was previously appreciated and reveals novel paths to study. Our graphical representations of the function-based global network will be a valuable resource to model new research findings.
ACCESSION #
38122971

 

Related Articles

  • Mature Peripheral RPE Cells Have an Intrinsic Capacity to Proliferate; A Potential Regulatory Mechanism for Age-Related Cell Loss. Kokkinopoulos, Ioannis; Shahabi, Golnaz; Colman, Alan; Jeffery, Glen // PLoS ONE;2011, Vol. 6 Issue 4, p1 

    Background: Mammalian peripheral retinal pigmented epithelium (RPE) cells proliferate throughout life, while central cells are senescent. It is thought that some peripheral cells migrate centrally to correct age-related central RPE loss. Methodology/Principal Findings: We ask whether this...

  • Seminal plasma induces global transcriptomic changes associated with cell migration, proliferation and viability in endometrial epithelial cells and stromal fibroblasts. Chen, Joseph C.; Johnson, Brittni A.; Erikson, David W.; Piltonen, Terhi T.; Barragan, Fatima; Chu, Simon; Kohgadai, Nargis; Irwin, Juan C.; Greene, Warner C.; Giudice, Linda C.; Roan, Nadia R. // Human Reproduction;Jun2014, Vol. 29 Issue 6, p1255 

    STUDY QUESTION How does seminal plasma (SP) affect the transcriptome of human primary endometrial epithelial cells (eEC) and stromal fibroblasts (eSF)? SUMMARY ANSWER Exposure of eEC and eSF to SP in vitro increases expression of genes and secreted proteins associated with cellular migration,...

  • Quantitative single-cell gene expression measurements of multiple genes in response to hypoxia treatment. Jia Zeng; Jiangxin Wang; Weimin Gao; Mohammadreza, Aida; Kelbauskas, Laimonas; Weiwen Zhang; Johnson, Roger H.; Meldrum, Deirdre R. // Analytical & Bioanalytical Chemistry;Nov2011, Vol. 401 Issue 1, p3 

    Cell-to-cell heterogeneity in gene transcription plays a central role in a variety of vital cell processes. To quantify gene expression heterogeneity patterns among cells and to determine their biological significance, methods to measure gene expression levels at the single-cell level are highly...

  • Next Generation Sequencing Analysis Reveals Segmental Patterns of microRNA Expression in Mouse Epididymal Epithelial Cells. Nixon, Brett; Stanger, Simone J.; Mihalas, Bettina P.; Reilly, Jackson N.; Anderson, Amanda L.; Dun, Matthew D.; Tyagi, Sonika; Holt, Janet E.; McLaughlin, Eileen A. // PLoS ONE;8/13/2015, Vol. 10 Issue 8, p1 

    The functional maturation of mammalian spermatozoa is accomplished as the cells descend through the highly specialized microenvironment of the epididymis. This dynamic environment is, in turn, created by the combined secretory and absorptive activity of the surrounding epithelium and displays an...

  • Regulation of intestinal epithelial cells transcriptome by enteric glial cells: impact on intestinal epithelial barrier functions. Van Landeghem, Laurianne; Mahé, Maxime M.; Teusan, Raluca; Léger, Jean; Guisle, Isabelle; Houlgatte, Rémi; Neunlist, Michel // BMC Genomics;2009, Vol. 10, p507 

    Background: Emerging evidences suggest that enteric glial cells (EGC), a major constituent of the enteric nervous system (ENS), are key regulators of intestinal epithelial barrier (IEB) functions. Indeed EGC inhibit intestinal epithelial cells (IEC) proliferation and increase IEB paracellular...

  • Proliferative activity of extracellular HIV-1 Tat protein in human epithelial cells: expression profile of pathogenetically relevant genes. Bettaccini, Alessia A.; Baj, Andreina; Accolla, Roberto S.; Basolo, Fulvio; Toniolo, Antonio Q . // BMC Microbiology;2005, Vol. 5, p20 

    Background: Tat is being tested as a component of HIV vaccines. Tat activity has been mainly investigated on cells of lymphoid/hematopoietic lineages. HIV-1, however, is known to infect many different cells of both solid organs and mucosal surfaces. The activity of two-exon (aa 1-101) and...

  • PPARÏ’ deficiency results in reduced lung elastic recoil and abnormalities in airspace distribution. Simon, Dawn M.; Tsai, Larry W.; Ingenito, Edward P.; Starcher, Barry C.; Mariani, Thomas J. // Respiratory Research;2010, Vol. 11, p69 

    Background: Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear hormone receptor that regulates gene expression, cell proliferation and differentiation. We previously described airway epithelial cell PPARγ deficient mice that develop airspace enlargement with decreased tissue...

  • Characterization of primary mammary epithelial cells with loss of BRCA1 at a single cell level. Nakles, Rebecca E.; Millman, Sarah; Cabrera, M. Carla; Johnson, Peter; Mueller, Susette C.; Hoppe, Philipp S.; Schroeder, Timm; Furth, Priscilla A. // BMC Proceedings;2013, Vol. 7 Issue Suppl 2, p1 

    The article focuses on a research that was conducted to determine the association of the human caretaker gene BRCA1 with increased cell proliferation in human mammary epithelial cells. It informs that individual cell lifetimes were measured using Timm's Individual Cell Tracking Tool software....

  • Oncogenes: Suppressive organization. Seton-Rogers, Sarah // Nature Reviews Cancer;Oct2007, Vol. 7 Issue 10, p730 

    The article examines the role of the cells architecture in epithelial tissues. This architecture can regulate proliferation and apoptosis by the oncogene MYC. Chronic activation of MYC construct leads to increase proliferation and the formation of structures that are 1.4 times larger than...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics