02 BOOK OF ABSTRACTS .indd

Are AKR1C1 and AKR1C3 responsible for development
and progression of endometrial cancer?
Tina [muc 1 , Katja Kristan 1 , Gregor Bajc 1 , Ruth Rupreht 2 , Jasna [inkovec 3
and Tea Lani{nik Ri`ner 1
1
Institute of Biochemistry, Medical Faculty, University of Ljubljana, Ljubljana, Slovenia;
2
Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia; 3 Department of Obstetrics and
Gynecology, University Medical Centre, Ljubljana, Slovenia
Endometrial cancer is one of the most common malignancies in developed countries.
In Slovenia, this type of cancer ranks fourth among all women malignancies and the
incidence (29.1 cases per 100,000 predicted for 2005) is higher than that reported for the
Western Europe and USA. It is well known that estrogens unopposed by progesterone
present high risk for endometrial cancer. The hormone action can be regulated at
the receptor level and at the prereceptor level by enzymatic interconversions of
highly active hormones (estradiol, progesterone) with their inactive counterparts
(estrone, 20α-hydroxyprogesterone). The hyxdroxysteroid-dehydrogenases (HSD)
AKR1C1 and AKR1C3 are multifunctional enzymes which catalyze conversion at the
3-, 17-, and 20-position of estrogens, androgens and progestins. Since AKR1C1
is predominantly 20α−HSD and AKR1C3 possesses high 17β-HSD activity these
enzymes could be responsible for modulating the levels of bioactive estradiol and
progesterone in endometrium.
In our study, we analyzed the mRNA levels of AKR1C1 and AKR1C3 and the presence
of the AKR1C3 protein in endometrial cancer. We extracted RNA and protein fraction
from 16 specimens of endometrial cancer and adjacent normal endometrium of the
same patient. The same endometrial samples were formalin-fixed, paraffin embedded
and sectioned for histopathological analysis and immunohistochemical staining with
108p35
AKR1C3 antibody. Quantification by real-time PCR revealed higher expression of
AKR1C1 in 9 and AKR1C3 in 4 specimens of endometrial cancer. Western blot analysis
confirmed the latter findings at the protein level and also immunohistochemistry
demonstrated staining of AKR1C3 protein in cancerous endometrium but not in
normal tissue. Our recent data thus indicate that changes in AKR1C1 and AKR1C3
expression may be responsible for endometrial cancer development and progression
due to increased estradiol and/or decreased progesterone levels.