Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, whereas steroid sulfatase (STS) hydrolyzes estrone sulfate to estrone. Both EST and STS have been suggested to play important roles in regulating the in situ production of estrogens in human breast carcinoma tissues. However, the expression of EST has not been examined in breast carcinoma tissues, and the biological significance of EST and STS remains unknown. Therefore, in this study, we examined the expression of EST and STS in 35 specimens of human breast carcinoma tissues using immunohistochemistry, reverse transcription-PCR (RT-PCR), and enzymatic assay. EST and STS immunoreactivity was also correlated with various clinicopathological parameters, including prognosis to examine the biological significance of these enzymes in 113 breast carcinomas. EST and STS immunoreactivity was detected in carcinoma cells and significantly associated with their mRNA levels (P = 0.0027 and 0.0158, respectively), as measured by RT/real-time PCR, and enzymatic activities (P = 0.0005 and 0.0089, respectively) in 35 breast carcinomas. In breast cancer tissues examined by laser capture microdissection/RT-PCR analyses, the mRNA for EST was localized in both carcinoma and intratumoral stromal cells, whereas that of STS was detected only in carcinoma cells. Of the 113 invasive ductal carcinomas examined in this study, EST and STS immunoreactivity was detected in 50 and 84 cases (44.2 and 74.3%), respectively. In these cases, EST immunoreactivity was inversely correlated with tumor size (P = 0.003) or lymph node status (P = 0.0027). In contrast, STS immunoreactivity was significantly correlated with tumor size (P = 0.0047). Moreover, EST immunoreactivity was significantly associated with a decreased risk of recurrence or improved prognosis by both uni (P = 0.0044, and 0.0026, respectively) and multivariate (P = 0.0429 and 0.0149, respectively) analyses. STS immunoreactivity, however, was significantly associated with an increased risk of recurrence (P = 0.0118) and worsened prognosis (P = 0.0325) by univariate analysis. Results from our present study suggest that immunoreactivities for both EST and STS are associated with their mRNA level and enzymatic activity and that EST immunoreactivity is considered to be a potent prognostic factor in human breast carcinoma.
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PMID:Estrogen sulfotransferase and steroid sulfatase in human breast carcinoma. 1278 80

Steroid sulfatase (STS) hydrolyzes inactive estrone sulfate (E1-S) to estrone (E1), while estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to estrogen sulfates. They are considered to play important roles in the regulation of local estrogenic actions in various human tissues, however, their biological significance remains largely unknown. Therefore, we examined the expression of STS and EST in non-pathologic human tissues and breast carcinomas. STS expression was very weak except for the placenta, while EST expression was markedly detected in various tissues examined. In breast carcinoma tissues, STS and EST immunoreactivity was detected in carcinoma cells in 74 and 44% of cases, respectively, and was significantly associated with their mRNA levels and enzymatic activities. STS immunoreactivity was significantly correlated with the tumor size, and an increased risk of recurrence. EST immunoreactivity was inversely correlated with the tumor size or lymph node status. Moreover, EST immunoreactivity was significantly associated with a decreased risk of recurrence or improved prognosis. Our results suggest that EST is involved in protecting various peripheral tissues from excessive estrogenic effects. In the breast carcinoma, STS and EST are suggested to play important roles in the regulation of in situ estrogen production in the breast carcinomas.
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PMID:Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma. 1462 43

Intratumoral metabolism and synthesis of estrogens as a result of the interactions of various enzymes are considered to play very important roles in the pathogenesis and development of hormone dependent breast carcinoma. Among these enzymes, intratumoral aromatase plays as important role converting serum androgens to estrogens in situ, and serves as a source of estrogen, especially in postmenopausal patients with breast carcinoma. However, other enzymes such as the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes, estrogen sulfatase (STS) and estrogen sulfotransferase, also play pivotal roles in intratumoral estrogen production. The 17beta-hydroxysteroid dehydrogenase (17beta-HSD) isozymes catalyze the interconversion of estradiol (E2) and estrone (E1), and thereby serve to modulate the tissue levels of bioactive E2 in human breast carcinoma. 17Beta-HSD type 1 catalyzes primarily the reduction of estrone (E1) to estradiol (E2), whereas 17beta-HSD type 2 catalyzes primarily the oxidation of E2 to E1. In human breast disease, 17beta-HSD type 1 is expressed in proliferative disease without atypia, atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma. 17Beta-HSD type 2 has not been detected in any of these breast lesions. In addition, 17beta-HSD type 1 coexpression is significantly correlated with estrogen receptor status in invasive ductal carcinoma cases. These results indicate that breast carcinoma can effectively convert E1, produced as a result of in situ aromatization, to E2, a biologically potent estrogen, which exerts estrogenic actions on tumor cells through estrogen receptor, especially the alpha subtype in carcinoma cells. Therefore, inhibiting intratumoral 17beta-HSD type 1 is also considered to contribute to inhibition of cell proliferation by decreasing intratumoral estradiol. Estrogen sulfotransferase (EST; SULT 1E1 or STE gene) sulfonates estrogens to inactive estrogen sulfates, while steroid sulfatase (STS) hydrolyzes estrone sulfate (E1-S) to estrone. EST immunoreactivity was recently demonstrated to be significantly associated with a decreased risk of recurrence or improved prognosis by both uni- and multivariate analyses. STS immunoreactivity was significantly associated with an increased risk of recurrence by univariate analysis. These findings also suggest that EST and STS plays important roles in regulation of in situ estrogen production, and EST especially is a potent prognostic factor in human breast carcinoma. Therefore, the inhibition of intratumoral STS might also serve as an endocrine therapy in postmenopausal patients. It is also important to note that the status of intratumoral aromatase, 17beta-HSD type 1, EST and STS in human breast cancer tissues is variable and not necessarily correlated with each other, which suggests different potential sources of intratumoral estrogens among individual patients with breast cancer. These findings indicate that there are patients who could benefit more from inhibition of these intratumoral enzymes rather than aromatase inhibition as an endocrine therapy. Therefore, it will become very important to examine the intratumoral levels of 17beta-HSD type 1 and STS in the resected specimens of human breast carcinoma as potential targets of novel endocrine therapy in the near future.
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PMID:New development in intracrinology of breast carcinoma. 1675 6