Expression of mitochondrial regulators PGC1α and TFAM as putative markers of subtype and chemoresistance in epithelial ovarian carcinoma

Autor: Joseph W. Carlson, Marike Gabrielson, Maria C. Shoshan, My Björklund
Jazyk: angličtina
Rok vydání: 2014
Předmět:
endocrine system diseases
Cell
lcsh:Medicine
Mitochondrion
Bioinformatics
Biochemistry
Molecular Cell Biology
Basic Cancer Research
Medicine and Health Sciences
Cystadenocarcinoma
lcsh:Science
Aged
80 and over
Ovarian Neoplasms
Multidisciplinary
Obstetrics and Gynecology
Middle Aged
Prognosis
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
female genital diseases and pregnancy complications
DNA-Binding Proteins
Serous fluid
medicine.anatomical_structure
Oncology
Cytochemistry
Disease Progression
Adenocarcinoma
Female
Glycogen
Research Article
Signal Transduction
Adult
Biology
Mitochondrial Proteins
Cell Line
Tumor
medicine
Carcinoma
Cancer Detection and Diagnosis
Biomarkers
Tumor
Humans
Aged
lcsh:R
Gynecologic Cancers
Biology and Life Sciences
Cell Biology
TFAM
medicine.disease
Cystadenocarcinoma
Serous
Drug Resistance
Neoplasm
Cancer research
Women's Health
lcsh:Q
Ovarian cancer
Adenocarcinoma
Clear Cell
Transcription Factors
Zdroj: PLoS ONE, Vol 9, Iss 9, p e107109 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated with major metabolic alterations, notably altered mitochondrial function(s). Here, we report for the first time that the expression of the mitochondrial regulators PGC1α and TFAM varies between EOC subtypes; furthermore, we have identified a profile in clear-cell carcinoma consisting of undetectability of PGC1α/TFAM, and low ERα/Ki-67. By contrast, high-grade serous carcinomas were characterised by a converse state of PGC1α/TFAM, ERα positivity and a high Ki-67 index. Interestingly, loss of PGC1α/TFAM and ERα was found also in a non-clear cell EOC cell line made highly resistant to platinum in vitro. Similar to clear-cell carcinomas, these resistant cells also showed accumulation of glycogen. Altogether, our data provide mechanistic insights into the chemoresistant nature of ovarian clear-cell carcinomas. Furthermore, these findings corroborate the need to take into account the diversity of EOC and to develop subtype specific treatment strategies.
Databáze: OpenAIRE
Externí odkaz: