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Altered profile of E1-S transporters in endometrial cancer : lower protein levels of ABCG2 and OSTβ and up-regulation of SLCO1B3 expression
ID
Pavlič, Renata
(
Avtor
),
ID
Vidic, Suzana
(
Avtor
),
ID
Anko, Maja
(
Avtor
),
ID
Knific, Tamara
(
Avtor
),
ID
Büdefeld, Tomaž
(
Avtor
),
ID
Marton, Kristina
(
Avtor
),
ID
Sinreih, Maša
(
Avtor
),
ID
Poschner, Stefan
(
Avtor
),
ID
Jäger, Walter
(
Avtor
),
ID
Frković-Grazio, Snježana
(
Avtor
),
ID
Lanišnik-Rižner, Tea
(
Avtor
)
PDF - Predstavitvena datoteka,
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MD5: 786DE74B6841DD8B38B68A2D2513FFFE
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/1422-0067/22/8/3819
Galerija slik
Izvleček
Endometrial cancer (EC) is associated with increased estrogen actions. Locally, estrogens can be formed from estrone-sulphate (E1-S) after cellular uptake by organic anion-transporting polypeptides (OATP) or organic anion transporters (OAT). Efflux of E1-S is enabled by ATP Binding Cassette transporters (ABC) and organic solute transporter (OST)αβ. Currently, 19 E1-S transporters are known but their roles in EC are not yet understood. Here, we analysed levels of E1-S transporters in Ishikawa (premenopausal EC), HEC-1-A (postmenopausal EC), HIEEC (control) cell lines, in EC tissue, examined metabolism of steroid precursor E1-S, studied effects of OATPs’ inhibition and gene-silencing on E1-S uptake, and assessed associations between transporters and histopathological data. Results revealed enhanced E1-S metabolism in HEC-1-A versus Ishikawa which could be explained by higher levels of OATPs in HEC-1-A versus Ishikawa, especially 6.3-fold up-regulation of OATP1B3 (SLCO1B3), as also confirmed by immunocytochemical staining and gene silencing studies, lower ABCG2 expression and higher levels of sulfatase (STS). In EC versus adjacent control tissue the highest differences were seen for ABCG2 and SLC51B (OSTβ) which were 3.0-fold and 2.1-fold down-regulated, respectively. Immunohistochemistry confirmed lower levels of these two transporters in EC versus adjacent control tissue. Further analysis of histopathological data indicated that SLCO1B3 might be important for uptake of E1-S in tumours without lymphovascular invasion where it was 15.6-fold up-regulated as compared to adjacent control tissue. Our results clearly indicate the importance of E1-S transporters in EC pathophysiology and provide a base for further studies towards development of targeted treatment.
Jezik:
Angleški jezik
Ključne besede:
endometrial cancer
,
intracrinology
,
organic anion-transporting polypeptides
,
estrone-sulphate (E1-S)
,
sulfatase pathway
,
E1-S transporters
,
ATP-binding cassette transporters
,
organic solute transporters
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
MF - Medicinska fakulteta
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2021
Št. strani:
26 str.
Številčenje:
Vol. 22, iss. 8, art. 3819
PID:
20.500.12556/RUL-135333
UDK:
618.1
ISSN pri članku:
1422-0067
DOI:
10.3390/ijms22083819
COBISS.SI-ID:
58810371
Datum objave v RUL:
08.03.2022
Število ogledov:
1464
Število prenosov:
105
Metapodatki:
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Objavi na:
Gradivo je del revije
Naslov:
International journal of molecular sciences
Skrajšan naslov:
Int. j. mol. sci.
Založnik:
MDPI
ISSN:
1422-0067
COBISS.SI-ID:
2779162
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Začetek licenciranja:
07.04.2021
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
rak endometrija
,
intrakrinologija
,
organski polipeptidi
,
ki prenašajo anione
Projekti
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Številka projekta:
J3-8212
Naslov:
Vloga intrakrinega delovanja estrogenov pri hormonsko odvisnih boleznih – pomen za zdravljenje
Financer:
ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
Program financ.:
Young Researcher
Financer:
FWF - Austrian Science Fund
Številka projekta:
I 3417-B31
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