Model cell lines and tissues of different HGSOC subtypes differ in local estrogen biosynthesis

Renata Pavlič (Avtor), Marija Gjorgoska (Avtor), Tea Lanišnik-Rižner (Avtor)

Povzetek

Ovarian cancer (OC) is highly lethal and heterogeneous. Several hormones are involved in OC etiology including estrogens; however, their role in OC is not completely understood. Here, we performed targeted transcriptomics and estrogen metabolism analyses in high-grade serous OC (HGSOC), OVSAHO, Kuramochi, COV632, and immortalized normal ovarian epithelial HIO-80 cells. We compared these data with public transcriptome and proteome data for the HGSOC tissues. In all model systems, high steroid sulfatase expression and weak/undetected aromatase (CYP19A1) expression indicated the formation of estrogens from the precursor estrone-sulfate (E1-S). In OC cells, the metabolism of E1-S to estradiol was the highest in OVSAHO, followed by Kuramochi and COV362 cells, and decreased with increasing chemoresistance. In addition, higher HSD17B14 and CYP1A2 expressions were observed in highly chemoresistant COV362 cells and platinum-resistant tissues compared to those in HIO-80 cells and platinum-sensitive tissues. The HGSOC cell models differed in HSD17B10, CYP1B1, and NQO1 expression. Proteomic data also showed different levels of HSD17B10, CYP1B1, NQO1, and SULT1E1 between the four HGSOC subtypes. These results suggest that different HGSOC subtypes form different levels of estrogens and their metabolites and that the estrogen-biosynthesis-associated targets should be further studied for the development of personalized treatment.

Ključne besede

rak jajčnikov;serozni karcinom jajčnikov visoke stopnje;HIO-80;ovarian cancer;high-grade serous ovarian carcinoma;

Podatki

Jezik:	Angleški jezik
Leto izida:	2022
Tipologija:	1.01 - Izvirni znanstveni članek
Organizacija:	UL MF - Medicinska fakulteta
UDK:	618.1
COBISS:	108982787
ISSN:	2072-6694
Št. ogledov:	31
Št. prenosov:	3
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	rak jajčnikov;serozni karcinom jajčnikov visoke stopnje;HIO-80;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 1-22
Letnik:	ǂVol. ǂ14
Zvezek:	ǂno. ǂ11
Čas izdaje:	2022
DOI:	10.3390/cancers14112583
ID:	18572688