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Investigation of centrosome amplification and cytokinesis regression in chrysotile treated culture cells

Grant number: 13/07515-6
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Start date: August 01, 2013
End date: September 30, 2013
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Glaucia Maria Machado Santelli
Grantee:Beatriz de Araujo Cortez
Supervisor: Stephen J. Doxsey
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Institution abroad: University of Massachusetts Medical School (UMMS), United States  
Associated to the scholarship:09/17140-4 - DIFFERENT APPROACHES TO UNDERSTANDING ANEUPLOIDY: INTERFERING ON MITOSIS USING CHRYSOTILE, VINCRISTINE AND TELOMERE SHORTENING., BP.DR

Abstract

Aneuploidy is a characteristic associated with aggressiveness of solid tumors. Aneuploid cells can result from many errors during mitosis, including defects in chromatid cohesion, abnormalities in the mitotic checkpoint, errors or hyperstabilized interactions between microtubules and kinetochores connection, centrossome amplification, multipolar mitosis and cytokinesis failure. As many processes are related to aneuploidy, and aneuploidy can promote both tumor formation and suppression, many efforts are being made to identify each errors in mitosis are related to viable aneuploid cell formation and each ones are related to cell death. Centrosome amplification has been extensively studied due to its involvement in aneuploid cell formation, its strong presence in tumor cells and also because centrosome is considered today as a reaction center that organizes spatial-temporally cell cycle elements. Regarding cytokinesis failure, besides being one of the causes centrosome amplification, it is responsible for forming tetraploid cells, which is considered an unstable step between normal DNA content and aneuploidy, favoring tumor formation. Our group has previously showed that chrysotile fibers, a type of asbestos, induce multipolar mitosis and aneuploid cells formation. In the present PhD project it was shown that the compound leads to formation of supernumerary centrossomes, cytokinesis regression and subsequent tetraploidization. At the moment it is interesting to investigate how centrosome amplification occurs in the system, and to study the causes of cytokinesis regression in cells treated with chrysotile. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CORTEZ, BEATRIZ ARAUJO; TEIXEIRA, PAULA REZENDE; REDICK, SAMBRA; DOXSEY, STEPHEN; MACHADO-SANTELLI, GLAUCIA MARIA. Multipolar mitosis and aneuploidy after chrysotile treatment: a consequence of abscission failure and cytokinesis regression. ONCOTARGET, v. 7, n. 8, p. 8979-8992, . (13/07515-6, 09/17140-4)