Different approaches to understand aneuploidy: interfering with mitosis using chrysotile and vincristine

Author(s)

Beatriz de Araujo Cortez

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2014-08-22

Examining board members

Glaucia Maria Machado Santelli; Alison Colquhoun; Luciana Amaral Haddad; Durvanei Augusto Maria; Angela Maria Vianna Morgante

• Advisor: Glaucia Maria Machado Santelli

Abstract

Aneuploidy is a feature of solid tumors. Aneuploid cells result from errors during mitosis, such as centrosome amplification, multipolar mitosis and cytokinesis abnormalities. The capability of aneuploidy to promote and to suppress tumorigenesis has driven the efforts to characterize mitotic errors that form viable and not viable aneuploid cells. We have previously shown that chrysotile, an asbestos fiber, and vincristine, a chemotherapeutic agent, are able to induce aneuploidy. Now we directed our focus to discover possible mechanisms involved in aneuploid cell formation. Herein we evaluated centrosome morphology, chromosome number, and origins and fates of multipolar mitosis after chrysotile and vincristine treatment. Chrysotile fibers, in normal and cancer cells, led to mislocalization of proteins involved in abscission, which resulted in cytokinesis regression and tetraploid cells. These cells were able to enter cell cycle, giving rise to multipolar mitosis and aneuploid cells. Vincristine treatment led to specific and common responses in normal and cancer cells. During metaphase arrest, pericentrosomal matrix was fragmented, and the cells could be conducted to mitotic slippage in both lineages. However, normal tetraploid cells could not progress through cell cycle and neither to form multipolar mitosis, while cancer tetraploid cells showed Aurora A overexpression, structural and numerical centrosome abnormalities, multipolar mitosis and high levels of aneuploidy. The results showed that cancer cells could proliferate even after several mitotic errors, while normal cells could only overcome errors induced by chrysotile treatment (AU)

• FAPESP's process: 09/17140-4 - DIFFERENT APPROACHES TO UNDERSTANDING ANEUPLOIDY: INTERFERING ON MITOSIS USING CHRYSOTILE, VINCRISTINE AND TELOMERE SHORTENING.
• Grantee: Beatriz de Araujo Cortez
• Support Opportunities: Scholarships in Brazil - Doctorate