Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells

Yamamoto, Takatsugu; Kitawaki, Jo; Urabe, Mamoru; Honjo, Hideo; Tamura, Takeyuki; Noguchi, Toshifumi; Okada, Hiroji; Sasaki, Hiroshi; Tada, Akio; Terashima, Y; Nakamura, Junji; Yoshihama, Makoto

doi:10.1016/0960-0760(93)90251-q

Cited by 80 publications

(50 citation statements)

References 9 publications

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“…It was reported that steroid sulfatase activities in endometrial cancer tissues were significantly higher than those in normal endometrial tissues (17). In addition, estrogen sulfotransferase activities were reported to be highest during the secretory phase of the menstrual cycle (40,41).…”

Section: Discussionmentioning

confidence: 99%

“…The SUPERSCRIPT Preamplification system reverse transcription kit (Life Technologies, Inc.) was used in the synthesis and amplification of cDNA. cDNA was synthesized from total RNA (2 g) using 25 ng/L oligo(dT) [12][13][14][15][16][17][18] primer (Life Technologies, Inc., Gaithersburg, MD) on a PTC-200 Peltier Thermal Cycler DNA Engine (MJ Research, Inc., Watertown, MA). To test for the presence of genomic DNA contamination, we performed the reverse transcription step in the absence of SUPER-SCRIPT II RNase H Ϫ Reverse Transcriptase (Life Technologies, Inc.,) followed by PCR.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, it is suggested that estrogen sulfotransferase, especially the balance between the levels of intratumoral steroid sulfatase and estrogen sulfo-transferase, may also play an important role in the regulation of in situ estrogen levels in human endometrial carcinoma. Steroid sulfatase and estrogen sulfotransferase activities have been examined in estrogen-dependent neoplasms such as endometrial and breast cancers (17). However, to date, steroid sulfatase and estrogen sulfotransferase mRNA and protein expressions have not been examined in human endometrial carcinoma.…”

Section: Introductionmentioning

confidence: 99%

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Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma

Utsunomiya¹,

Itō²,

Suzuki

et al. 2004

Clinical Cancer Research

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Purpose: Intratumoral metabolism and synthesis of estrogens are considered to play important roles in the pathogenesis and/or development of human endometrial carcinoma. Steroid sulfatase hydrolyzes biologically inactive estrogen sulfates to active estrogens, whereas estrogen sulfotransferase sulfonates estrogens to estrogen sulfates. However, the status of steroid sulfatase and/or estrogen sulfotransferase in human endometrial carcinoma has not been examined.Experimental Design: We first examined the expression of steroid sulfatase and estrogen sulfotransferase in 6 normal endometrium and 76 endometrial carcinoma using immunohistochemistry to elucidate the possible involvement of steroid sulfatase and estrogen sulfotransferase. We then evaluated the enzymatic activity and the semiquantitative analysis of mRNA using reverse transcription-PCR in 21 endometrial carcinomas. We correlated these findings with various clinicopathological parameters including the expression of aromatase, 17␤-hydroxysteroid dehydrogenase type 1 and type 2.Results: Steroid sulfatase and estrogen sulfotransferase immunoreactivity was detected in 65 of 76 (86%) and 22 of 76 (29%) cases, respectively. Results of immunoreactivity for steroid sulfatase and estrogen sulfotransferase were significantly correlated with those of enzymatic activity and semiquantitative analysis of mRNA. No significant correlations were detected among the expression of the enzymes involved in intratumoral estrogen metabolism. There was a significant correlation between steroid sulfatase/estrogen sulfotransferase ratio and clinical outcomes of the patients. However, there were no significant differences between steroid sulfatase or estrogen sulfotransferase and estrogen receptor, progesterone receptor, Ki67, histologic grade, or clinical outcomes of the patients.Conclusions: Results of our study demonstrated that increased steroid sulfatase and decreased estrogen sulfotransferase expression in human endometrial carcinomas may result in increased availability of biologically active estrogens and may be related to estrogen-dependent biological features of carcinoma.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma

Utsunomiya¹,

Itō²,

Suzuki

et al. 2004

Clinical Cancer Research

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“…Increased oestrone sulphatase activity in endometrial cancer tissue has also been detected (Yamamoto et al 1993 Oestrone-3-O-methyhhiophosphonate…”

mentioning

confidence: 93%

The development of steroid sulphatase inhibitors

Reed¹,

Purohit²,

Woo³

et al. 1996

Endocrine Related Cancer

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“…Thus, inhibiting STS activity in men with prostate cancer may reduce not only the production of testosterone from DHEAS but also androstenediol. STS activity is increased in endometrial cancer tissue, so its inhibition may also have therapeutic potential, by reducing estrogen synthesis, in this hormone-dependent cancer [22].…”

Section: Sts Inhibitors In Prostate and Endometrial Cancersmentioning

confidence: 99%

Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer

et al. 2007

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Key Words. Breast cancer • Estrogen • Estrone sulfate • Steroid sulfatase • Sulfatase inhibitor LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the role of steroid sulfatase in regulating estrogen production in postmenopausal women.2. Describe the potential of steroid sulfatase inhibition in cancer therapy.3. Discuss a potential new endocrine therapy for patients progressing on aromatase.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTInhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase (STS) activity is much higher than aromatase activity in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. STS hydrolyzes steroid sulfates, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS), to estrone and DHEA, which can be converted to steroids with potent estrogenic properties, that is, estradiol and androstenediol, respectively. Several potent irreversible STS inhibitors have now been identified, including STX64 (BN83495), a tricyclic sulfamate ester. This drug recently completed the first-ever trial of this new type of therapy in postmenopausal women with estrogen receptor-positive metastatic breast cancer. STX64, tested at 5-mg and 20-mg doses, was able to almost completely block STS activity in peripheral blood lymphocytes and tumor tissues. Inhibition of STS activity was associated with significant reductions in serum concentrations of androstenediol and estrogens. Unexpectedly, serum androstenedione concentrations also decreased by up to 86%, showing that this steroid, which is the main substrate for the aromatase in postmenopausal women, is derived mainly from the peripheral conversion of DHEAS. Of eight patients who completed therapy, five showed evidence of stable disease for up to 7.0 months. This new endocrine therapy offers considerable potential for the treatment of hormone-dependent breast cancer in postmenopausal women.

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Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells

Cited by 80 publications

References 9 publications

Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma

Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma

The development of steroid sulphatase inhibitors

Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer

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