Avtor/Urednik		Lanišnik-Rižner, Tea; Šmuc, Tina; Rupreht, Ruth; Šinkovec, Jasna; Penning, Trevor M
Naslov		AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer
Tip		članek
Vir		Mol Cell Endocrinol
Vol. in št.		Letnik 248, št. 1-2
Leto izdaje		2006
Obseg		str. 126-35
Jezik		eng
Abstrakt		Endometrial cancer is the most common malignancy of the female genital tract. Its incidence correlates with prolonged estrogen stimulation unopposed by progesterone or synthetic progestins. Estrogen and progestin action is regulated at the pre-receptor level, by interconversion of active hormones (estradiol (E2), progesterone (P)) with their inactive counterparts (estrone (El), 20alfa-hydroxyprogesterone (20alfa-OHP)) in target tissues. Expression of enzymes that control the ratio of E2 and P may thus play role in the disease process. We first confirmed that AKR1C1 (human 20alfa-hydroxysteroid dehydrogenase) in a cellular context inactivates P by forming 20alfa-OHP but does not catalyze the reverse reaction. We next examined the expression of AKR1C1 and AKR1C3 (type 5 17beta-hydroxysteroid dehdyrogenase) in 16 paired specimens of endometrial cancer and adjacent normal endometrium. Quantification by isoform specific real-time PCR revealed higher expression of AKR1C1 in nine specimens and higher expression of AKR1C3 in four specimens of endometrial cancer. Importantly, upregulation of both enzymes in the same specimen was observed. Since AKR1C1 inactivates P its elevated expression in diseased endometrium may contribute to diminished protection by P, while eleveated expression of AKR1C3 which forms E2 in vivo, may contribute to the enhanced estrogen action. It is suggested that the expression of AKR1C1 and AKR1C3 in endometrial cancer will govern the ratio of P:E2
Deskriptorji		ENDOMETRIAL NEOPLASMS ESTROGENS PROGESTERONE PROGESTATIONAL HORMONES, SYNTHETIC ESTRADIOL TRANSFECTION HYDROXYPROGESTERONES 20-HYDROXYSTEROID DEHYDROGENASES 17-HYDROXYSTEROID DEHYDROGENASES POLYMERASE CHAIN REACTION