Contributor:

Szeliga, Monika (Promotor)

Publisher:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN

Place of publishing:

Warszawa

Description:

Bibliografia zawiera 142 pozycje ; 108 s.: tabl., wykr., ryc. ; 30 cm

Degree name:

doktor

Level of degree:

2

Degree discipline :

biologia medyczna

Type of object:

Thesis

Abstract:

Glutamine (Gln) and glutamate (Glu)play a crucial role in the metabolism of glioblastoma (GBM, WHO IV).Glutamine (GA) is an enzyme which converts Gln to Glu and ammonia.There are two genes coding for human GA: the GLS gene encodes kidney-type isoforms (transcripts KGA and GAC), and the GLS2 gene codedfor liver-type isoforms (transcripts GAB and LGA). Deregulated expression and/or activity of GA isoforms is a characteristic feature of many cancer cell lines and tumor of different orgin. In GBM GLS expression is abundant, whereas expression of GLS2 is hardly detectable. Transfection of human GBM T98G cells with GAB sequence decreased their proliferation and migration ability and sensitized them oxidative stress. It was tempting to examine the effects of transfection with GAB on biological properties of human GBM cell lines varying with respect to the genetic background and to shed some light on the molecular mechanism underlying the GAB-mediated phenotypic changes. Literature data suggest that GAB besides enzymtic function also can modulate gene exprssion and/or signal transduction. Transfection of T98G cell with GAB deregulated expression of several genes some of which code for proteins belonging to WNT signaling pathway,e.g. GATA3 GENE. In turn, a recent study revealed that a hepatocellular carcinoma cell exogenous GAB is a negative regulator of AKT signaling pathway.The hypothesis of dissertation assumes the changes in biological properties of GBM cells transfected with GAB arise from modulation of the expression level and/or activity of proteins associated with WNTand AKT pathways.The obtained results revealed that transfection of human GBM cell lines: T98G, U87MG, LN229 with the sequence encoding GAB reduces their surival, proliferation index and colony formation ability.Moreover , exogenous GAB in T98G and LN229 cells inhibited the migration abilties of these cells.These observations suggest that exogenous GAB suppresses mentioned cell properties regardlesss of the genetic profile and tumorigenic potential of cells.

Relation:

Prace doktorskie.

Format:

application/pdf

Resource Identifier:

oai:rcin.org.pl:72006

Source:

IMDiK PAN, call no. ZS 394 ; click here to follow the link

Language:

pol

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego Polskiej Akademii Nauk

Original in:

Library of the Mossakowski Medical Research Institute PAS

Projects co-financed by:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Access:

Open