Expression of COX-2 and steroid converting enzymes in breast cancer.
COX-2 is upregulated in many breast tumors, and one of the products of COX-2 is PGE2 that is suggested to upregulate aromatase through cAMP signaling in breast cancer. Although aromatase can increase the estrogen levels in tumors, 17beta-hydroxysteroid dehydrogenase (17HSD) activity is finally needed for the estrone/estradiol regulation. The aim of this study was to investigate if the protein expression of enzymes involved in estrogen synthesis shows covariation with the expression of COX-2. We also wanted to correlate these results with prognosis. We analyzed the expression of COX-2, aromatase, 17HSD1 and 17HSD2 with immunohistochemistry using tissue microarrays composed of 356 primary breast tumors. In the present study COX-2 was correlated to aromatase (P<0.00001), 17HSD1 (P=0.0073), and 17HSD2 (P<0.00001). Patients with ER positive tumors expressing low amounts of 17HSD2 had decreased breast cancer survival (P=0.013). Elevated expression of COX-2 and aromatase was more frequent among larger tumors (P=0.017 and P=0.013). COX-2 expression correlates with the levels of the examined steroid converting enzymes and may contribute to increased estrogen levels in the tumor. In breast cancer cells, the regulatory function of 17HSD2 could be lost, and in the present study patients with low or non-detectable levels of 17HSD2 had worse prognosis than had breast cancer patients with higher levels of the enzyme.
Gunnarsson
Cecilia
C
Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Sweden. cecilia.gunnarsson@lio.se
Jansson
Agneta
A
Holmlund
Birgitta
B
Ferraud
Lilianne
L
Nordenskjöld
Bo
B
Rutqvist
Lars Erik
LE
Skoog
Lambert
L
Stål
Olle
O
D015067:17-Hydroxysteroid Dehydrogenases / Q000032:analysis* / Q000378:metabolism; D001141:Aromatase / Q000032:analysis* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000378:metabolism; D004960:Estradiol Dehydrogenases; D005260:Female; D006801:Humans; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism
D011960:Receptors, Estrogen; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D004960:Estradiol Dehydrogenases; C523763:HSD17B2 protein, human; D001141:Aromatase; D051546:Cyclooxygenase 2