17β-Hydroxysteroid Dehydrogenase Type 1 Is an Independent Prognostic Marker in Breast Cancer

Oduwole, Olayiwola; Yan, Li; Isomaa, Veli; Mäntyniemi, Anne; Pulkka, Anitta E.; Soini, Ylermi; Vihko, Pirkko

doi:10.1158/0008-5472.can-04-0446

Cited by 109 publications

(103 citation statements)

References 37 publications

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“…In humans, the closely related 17β-hydroxysteroid dehydrogenase is responsible for sex steroid metabolism (conversion of active estradiol to the less potent estrone) in normal and tumor tissues. It has been found to be up-regulated in breast tumors (Oduwole et al 2004) and, conversely, has also been found to be reduced in colonic tumors (English et al 1999). The apparent increase in expression of 3β-hydroxysteroid dehydrogenase in HC from female fish may indicate estrogen exposure and subsequent estrogen inactivation, and may be an important mechanism in the pathogenesis of HC.…”

Section: Discussionmentioning

confidence: 95%

Gene expression analyses of hepatocellular adenoma and hepatocellular carcinoma from the marine flatfish Limanda limanda

Small¹,

Williams²,

Sturve³

et al. 2010

Dis. Aquat. Org.

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At selected sites around the UK, the offshore sentinel flatfish species dab Limanda limanda are found to contain elevated levels of macroscopic liver tumors. Previous proteomic and metabolomic studies have demonstrated that differences exist between tumor and non-tumor tissues; however, these differing features were not identified, and little is known about the changes at the gene expression level, or whether prognostic markers are present and can be identified. A flounder Platichthys flesus custom cDNA microarray and RT-PCR were used to investigate hepatic mRNA expression in the histologically confirmed tumors, hepatocellular adenoma (HA) and hepatocellular carcinoma (HC) from dab, and in adjacent normal tissue from the same fish. Differences in gene expression were observed between tumor and normal tissues, and between tumor types. A class-prediction approach using 50 transcripts revealed sufficient group-specific expression profiles to allow segregation of samples dependent on their tumor type or the sex of the host. Vitellogenins were found to display the greatest induction (up to 500-fold induction) in some HC tumors from female fish and in both HA and HC tumors from males. To the best of our knowledge, this is the first report of the association of vitellogenin expression with tumors of wild fish.

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Section: Discussionmentioning

confidence: 95%

Gene expression analyses of hepatocellular adenoma and hepatocellular carcinoma from the marine flatfish Limanda limanda

Small¹,

Williams²,

Sturve³

et al. 2010

Dis. Aquat. Org.

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“…There is only one study that has investigated the prognostic importance of 17HSD5 in breast cancer. The authors found that patients with high 17HSD5 expression in the tumor had a worse prognosis than the group with low or no expression (8). The importance of 17HSD5 in breast cancer needs to be further clarified.…”

Section: Introductionmentioning

confidence: 98%

“…The SDR family consists of oxidoreductases that participate in the metabolism of steroids, prostaglandins, and retinoids (4). In breast tissue, several 17HSD family members have been reported to be present, such as 17HSD1, 17HSD2, 17HSD5, and 17HSD12 (5)(6)(7)(8)(9)(10)(11). Although 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far (7,8,10,11), it is possible that other hormone-regulating 17HSD enzymes may have a significant role in hormone-dependent tumors.…”

Section: Introductionmentioning

confidence: 99%

17β-Hydroxysteroid Dehydrogenase 14 Affects Estradiol Levels in Breast Cancer Cells and Is a Prognostic Marker in Estrogen Receptor–Positive Breast Cancer

Jansson¹,

Gunnarsson

Cohen³

et al. 2006

Cancer Research

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Estrogens have an important role in the progression of breast cancer. The 17B-hydroxysteroid dehydrogenase (17HSD) family has been identified to be of significance in hormonedependent tissues. 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far, but it is possible that other hormone-regulating enzymes have a similar role. 17HSD5 and 17HSD12 are associated with sex steroid metabolism, and 17HSD14 is a newly discovered enzyme that may be involved in the estrogen balance. The mRNA expression of 17HSD5, 17HSD12, and 17HSD14 were analyzed in 131 breast cancer specimens by semiquantitative real-time PCR. The results were compared with recurrencefree survival and breast cancer-specific survival of the patients. The breast cancer cell lines MCF7, SKBR3, and ZR75-1 were transiently transfected with 17HSD14 to investigate any possible effect on estradiol levels. We found that high 17HSD5 was related to significantly higher risk of late relapse in estrogen receptor (ER)-positive patients remaining recurrence-free later than 5 years after diagnosis (P = 0.02). No relation to 17HSD12 expression was found, indicating that 17HSD12 is of minor importance in breast cancer. Patients with ER-positive tumors with high expression levels of 17HSD14 showed a significantly better prognosis about recurrence-free survival (P = 0.008) as well as breast cancerspecific survival (P = 0.01), confirmed by multivariate analysis (P = 0.04). Transfection of 17HSD14 in the human breast cancer cells MCF7 and SKBR3 significantly decreased the levels of estradiol, presenting an effect of high expression

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“…Thin-layer chromatography (TLC) was performed on 0. 25 C respectively. Duplication of NMR signals was generally recorded for THP derivatives.…”

Section: Generalmentioning

confidence: 98%

“…Furthermore, a study revealed that the reductive activity (E 1 into E 2 ) is higher in malignant breast tumours whereas the oxidative pathway (E 2 into E 1 ) is dominant in normal breast cell [22]. 17b-HSD1 mRNA has been detected in malignant breast tumours by in situ hybridization, immunohistochemistry and reverse transcription-PCR [23][24][25]. It was also demonstrated that 17b-HSD1 plays a role in the local biosynthesis of estrogen in the breast, especially in postmenopausal women, after the ovaries have ceased to produce estrogen [26,27].…”

Section: Introductionmentioning

confidence: 99%

Improved synthesis of EM-1745, preparation of its C17-ketone analogue and comparison of their inhibitory potency on 17β-hydroxysteroid dehydrogenase type 1

Bérubé

Poirier

2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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Endocrine therapies are widely used for the treatment of estrogen-sensitive diseases. 17b-hydroxysteroid dehydrogenase type 1 (17b-HSD1) is involved in the last step of the biosynthesis of potent estrogen estradiol (E 2 ). This enzyme catalyzes the reduction of the C17-ketosteroid estrone (E 1 ) into the C17b-hydroxy steroid E 2 using the cofactor NAD(P)H. The X-ray analysis of E 2 /adenosine bisubstrate inhibitor EM-1745 proven that this compound interacts with both the substrate-and the cofactor-binding sites. However, E 1 is a better substrate of 17b-HSD1 than E 2 . Thus, in order to improve the inhibitory potency of EM-1745, the C17-ketone analogue was prepared. During this work, a new and more efficient method for synthesizing EM-1745 was developed using an esterification and a cross-metathesis as key steps. Contrary to what was expected, the C17-ketone analogue of EM-1745 is a less potent inhibitor (IC 50 ¼ 12 nM) than the C17-alcohol (IC 50 ¼ 4 nM) in homogenated HEK-293 cells overexpressing 17b-HSD1. Our results contribute to the knowledge of an unexpected observation: the C17-ketone steroidal inhibitors of 17b-HSD1 are less potent than their corresponding C17-alcohol derivatives.

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17β-Hydroxysteroid Dehydrogenase Type 1 Is an Independent Prognostic Marker in Breast Cancer

Cited by 109 publications

References 37 publications

Gene expression analyses of hepatocellular adenoma and hepatocellular carcinoma from the marine flatfish Limanda limanda

Gene expression analyses of hepatocellular adenoma and hepatocellular carcinoma from the marine flatfish Limanda limanda

17β-Hydroxysteroid Dehydrogenase 14 Affects Estradiol Levels in Breast Cancer Cells and Is a Prognostic Marker in Estrogen Receptor–Positive Breast Cancer

Improved synthesis of EM-1745, preparation of its C17-ketone analogue and comparison of their inhibitory potency on 17β-hydroxysteroid dehydrogenase type 1

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