Institutional creator:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Contributor:

Więckowski, Mariusz Roman (1972– ) : Supervisor

Publisher:

Instytut Biologii Doświadczalnej im. M. Nenckiego PAN

Place of publishing:

Warszawa

Description:

255 pages : illustrations ; 30 cm ; Bibliography ; Summary in English

Degree grantor:

Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN

Type of object:

Thesis

Abstract:

Mitochondria carry out a variety of important cellular functions including ATP synthesis as well as reactive oxygen species production. They are also implicated in many crucial cellular processes, in regulation of the levels of several substantial for the cell metabolites and e.g., in the initiation of the apoptosis process. Therefore, it is not surprising that mitochondria of tumor cells could be a potential target in chemotherapy. Substantial number of evidence indicate that both, apoptosis and reactive oxygen species production involve a small p66Shc adaptor protein, which demonstrates the unique prooxidative properties comparing to other ShcA family members (p46Shc and p52Shc). Taking into account the fact that p66Shc can play a dual role as a negative regulator of proliferation and as oxidative stress sensor, p66Shc seems to be a promising target concerning cancer proliferation, tumor progression and chemotherapeutic treatment.My doctoral dissertation presents a comprehensive evaluation of the role of p66Shc protein in mitochondrial physiology of breast cancer cells. Moreover, describes response of these cells to chemotherapeutic treatment with the use of doxorubicin agent. Furthermore, the use of human breast cancer cell lines (MDA-MB-231 and MCF-7) and their genetically modified clones presenting different level of p66Shc protein allowed me to demonstrate how the p66Shc protein can affect the mitochondrial metabolism of human breast cancer cells.The comparative analysis of two breast cancer cell lines characterized with relatively different level of p66Shc and their noncancerous equivalents (MCF-10) have revealed that both tumor cell lines: MDA-MB-231 and MCF-7 being two various subtypes of breast cancer and characterized with different metastasis abilities significantly differ in most of studied cellular parameters. Furthermore, changes in the level of p66Shc protein (in individual breast cancer cell lines) exert different effects in the same clones respectively: MDA-MB-231 and MCF-7 tumor cell lines (overexpressing p66Shc protein, overexpressing of Ser36-mutated p66Shc as well as knockout of p66Shc). Knocking out p66Shc in both breast cancer cell lines caused significant changes observed mostly in mitochondrial physiological parameters. Interesting, in both of examined breast cancer cell lines, I did not found positive correlation between overexpression of p66Shc (containing serine 36 residue responsible for the prooxidative properties of the p66Shc protein) and the level of reactive oxygen species. I have shown that clone of MDA-MB-231 (which is more metastatic type of breast cancer comparing to MCF-7 cell line) lacking p66Shc protein represents the most glycolytic phenotype comparing to other

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:236541

Source:

IBD PAN, call no. 20076

Language:

pol

Language of abstract:

eng

Digitizing institution:

Nencki Institute of Experimental Biology of the Polish Academy of Sciences

Original in:

Library of the Nencki Institute of Experimental Biology PAS

Access:

Open