Abstract | BACKGROUND: EXPERIMENTAL DESIGN: We initially explored whether circulating levels of estrogens, measured by validated mass spectrometry assays, differ in women with endometrial cancer (n = 126) compared with healthy women (n = 110). We then evaluated by quantitative real-time PCR from purified RNA whether the expression profile of 19 estrogen-related synthesis and metabolic genes is modified in peritumoral normal endometrium (n = 36) compared with tumoral (n = 49) tissues. RESULTS: In endometrial cancer cases, circulating levels of E(1), E(2), and E(1)-S were significantly higher compared with unaffected controls. In agreement with plasma levels, findings support an enhanced biosynthesis of E(2) in tumors. The expression of E(2) biosynthesis pathways [E(1)-S ( sulfatase) --> E(1) (17beta-hydroxysteroid dehydrogenase) --> E(2)] was shown to predominate in peritumoral normal endometrium and was significantly increased in tumors. In addition, the inactivation pathways mediated by several uridine diphosphate-glucuronosyltransferases were also enhanced in endometrial tumors compared with peritumoral normal endometrium. CONCLUSION: We concluded that the higher levels of circulating estrogens in women with endometrial cancer are likely associated with an imbalance of multiple biotransformation pathways in endometrial tumor tissues.
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Authors | Johanie Lépine, Etienne Audet-Walsh, Jean Grégoire, Bernard Têtu, Marie Plante, Vincent Ménard, Pierre Ayotte, Jacques Brisson, Patrick Caron, Lyne Villeneuve, Alain Bélanger, Chantal Guillemette |
Journal | The Journal of clinical endocrinology and metabolism
(J Clin Endocrinol Metab)
Vol. 95
Issue 6
Pg. 2689-98
(Jun 2010)
ISSN: 1945-7197 [Electronic] United States |
PMID | 20371658
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Complementary
- Enzymes
- Estrogens
- Gonadal Steroid Hormones
- RNA
- 17-Hydroxysteroid Dehydrogenases
- Glucuronosyltransferase
- Deoxyribonucleases
- Sulfatases
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Topics |
- 17-Hydroxysteroid Dehydrogenases
(metabolism)
- Aged
- DNA, Complementary
(biosynthesis, genetics)
- Deoxyribonucleases
(chemistry)
- Endometrial Neoplasms
(blood, enzymology)
- Endometrium
(metabolism)
- Enzymes
(biosynthesis, metabolism)
- Estrogens
(biosynthesis, blood)
- Female
- Glucuronosyltransferase
(metabolism)
- Gonadal Steroid Hormones
(blood)
- Humans
- Middle Aged
- RNA
(biosynthesis, isolation & purification)
- Reverse Transcriptase Polymerase Chain Reaction
- Sulfatases
(metabolism)
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