PhD Scientific Days 2017

Budapest, 11-12 April 2017

Oral Presentations: Oncology

Characterisation of metabolic and mtor activity in different breast cancer subtypes

Előadó neve

Dr. Petővári, Gábor

Előadó munkahelye

First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Előadó telefonszáma

0614591500/54430

Előadó e-mail címe

gaborpetovari@gmail.com

Az előadás címe

Characterisation of metabolic and mtor activity in different breast cancer subtypes

Szerző(k) neve és munkahelye

Gábor Petővári 1, Zoltán Hujber 1, Titanilla Dankó 1, Norbert Szoboszlai 2, Noémi Nagy1, Ildikó Krencz1, Annamária Tőkés3, Janina Kulka3, Judit Pápay1, Melinda Hajdu1, András Jeney1, Anna Sebestyén1,4
1 First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
2 Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary
3 Second Department of Pathology, Semmelweis University, Budapest, Hungary
4 Tumor Progression Research Group Joint Research Organization of Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

Szekció

Oral Presentations: Oncology

Data of the presenter

Supported by MTA Bolyai Grant (AS), ÚNKP-16-3 (NN) and NTP-NFTÖ-16 (ZH)

Doctoral School: Pathological Sciences
Program: Oncology
Supervisor: Anna Sebestyén
E-mail address: gaborpetovari@gmail.com
poster presentation (hungarian language)

Text of the abstract

Regulatory role of mTOR (mammalian target of rapamycin) kinase in cellular signalling network, especially the different role of mTORC1/C2 complexes are both involved in the alterations of tumour cell metabolism. mTOR and metabolic activity of tumour cells can influence the growth, survival and therapy resistance in different breast cancer subtypes.
The genetic heterogeneity is usually characterised, however, the metabolic profile analysis of different tumours, as breast cancers are still missing in recent studies.
In our work, the expressions of several metabolic transporter, enzymes and mTOR activity related proteins were studied by Western blot, ICC and IHC using breast cancer cell lines and human tissue samples. Furthermore, the metabolic phenotype, the substrate utilization and their alterations after different treatments were also analysed using LC-MS. The anti-tumour effects of these treatments were also evaluated in vitro.
Metabolic and mTORC1/C2 complex activity were detected in breast cancer cell lines and human tissue samples independently of their subtype differences. The glycolytic phenotype was accompanied by high mTORC1 related protein expression and high lactate level in the majority of the studied cell lines. While low level of p-S6 and high Rictor protein expression were found in cells which have characteristic intensive TCA cycle activity. The in vitro detected metabolic inhibitor sensitivity of breast carcinoma cells correlated to the characteristic metabolic profile and mTORC1/C2 activation. The selected metabolic IHC markers showed such differences in human breast cancer biopsies, as well. However, these require further investigations.
Our findings suggest that these differences in metabolic protein expressions may explain the differences in therapeutic sensitivity of same human breast cancers subtypes. The evaluation of mTOR activity and metabolic profile in different breast cancer subtypes may help to allow new and better ways to introduce therapeutic drug combinations and the early detection of resistance in the future therapy.

Kind

Szabad

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1269

Authors (legacy)

Gábor Petővári 1, Zoltán Hujber 1, Titanilla Dankó 1, Norbert Szoboszlai 2, Noémi Nagy1, Ildikó Krencz1, Annamária Tőkés3, Janina Kulka3, Judit Pápay1, Melinda Hajdu1, András Jeney1, Anna Sebestyén1,4
1 First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
2 Laboratory of Environmental Chemistry and Bioanalytics, Department of Analytical Chemistry, Institute of Chemistry, Eötvös Loránd University, Budapest, Hungary
3 Second Department of Pathology, Semmelweis University, Budapest, Hungary
4 Tumor Progression Research Group Joint Research Organization of Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary