Estrone sulfate and sulfatase activity in human breast cancer and endometrial cancer

Naitoh, Ken; Honjo, Hideo; Yamamoto, Takara; Urabe, Mamoru; Ogino, Yukiko; Yasumura, Tadaki; Nambara, Toshio

doi:10.1016/0022-4731(89)90408-1

Cited by 70 publications

(42 citation statements)

References 26 publications

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“…The concentration of intratumoral E 2 is higher in the endometrial cancer tissues than in normal endometrium (Naitoh et al 1989, Berstein et al 2003, and is regulated by estrogen-metabolizing enzymes such as aromatase, 17b-HSD types 2 and 5 (Ito et al 2006; Fig. 2C).…”

Section: Detection Of Er-activating Ability Of Stromal Cells In Endommentioning

confidence: 93%

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Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction

Matsumoto

Yamaguchi

Seino

et al. 2008

Endocrine Related Cancer

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The estrogen pathway plays an important role in the etiology of human endometrial carcinoma (EC). We examined whether estrogen biosynthesis in the tumor microenvironment promotes endometrial cancer. To examine the contribution of stromal cells to estrogen signaling in EC, we used reporter cells stably transfected with the estrogen response element (ERE) fused to the destabilized green fluorescent protein (GFP) gene. In this system, the endometrial cancer stromal cells from several patients activated the ERE of cancer cells to a variable extent. The GFP expression level increased when testosterone, a substrate for aromatase, was added. The effect was variably inhibited by aromatase inhibitors (AIs), although the response to AIs varied among patients. These results suggest that GFP expression is driven by estrogen synthesized by aromatase in the endometrial cancer stromal cells. In a second experiment, we constructed an adenovirus reporter vector containing the same construct as the reporter cells described above, and visualized endogenous ERE activity in primary culture cancer cells from 15 EC specimens. The GFP expression levels varied among the cases, and in most primary tissues, ERE activities were strongly inhibited by a pure anti-estrogen, fulvestrant. Interestingly, a minority of primary tissues in endometrial cancer showed ERE activity independent of the estrogen-ER pathway. These results suggest that AI may have some therapeutic value in EC; however, the hormonal microenvironment must be assessed prior to initiating therapy.

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Section: Detection Of Er-activating Ability Of Stromal Cells In Endommentioning

confidence: 93%

“…The estrogen level in EC tissue is higher than that in the endometrial tissue of healthy women (Naitoh et al 1989, Berstein et al 2003. Furthermore, estrogenmetabolizing enzymes such as aromatase, sulfatase, sulfotransferase, and 17b-hydroxysteroid dehydrogenases (17b-HSDs) exist in stromal cells adjacent to the tumor.…”

Section: Introductionmentioning

confidence: 99%

Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction

Matsumoto

Yamaguchi

Seino

et al. 2008

Endocrine Related Cancer

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“…In contrast, higher levels of oestrone sulphotransferase, which catalyses the formation of oestrone sulphate from oestrone, have been found in breast cancer samples which are positive for both oestrogen and progesterone receptors (Adams et al, 1979;Pewnim et al, 1980). Intratumoral oestrone sulphatase activity is higher than in surrounding normal breast tissue (Naitoh et al, 1989 Moreover, a comparative study of oestrone sulphatase and aromatase activities in human breast cancer samples suggested that the oestrone sulphatase pathway is the predominant source of intratumoral oestrogen production in post-menopausal women (Santner et al, 1984). Moreover, the biological effects demonstrated in response to physiological concentrations of oestrone sulphate in MCF-7 cell cultures provide further evidence of the relevance of this pathway in the production of intratumoral oestrogens in breast carcinoma tissues (Santner et al, 1993).…”

mentioning

confidence: 85%

“…Hydrolysis of oestrone sulphate to oestrone by human breast carcinoma tissue has been demonstrated by several groups (Wilking et al, 1980;Carlstrom et al, 1984;Prost et al, 1984;Santner et al, 1984;Naitoh et al, 1989). Wilking et al (1980) found oestrone sulphatase activity in all of 23 human breast carcinoma samples assayed; Prost et al (1984) found oestrone sulphatase activity in all of 21 tumours assayed, and Santner et al (1984) found oestrone sulphatase activity in all of 35 tumours assayed.…”

mentioning

confidence: 94%

Intratumoral oestrone sulphatase activity as a prognostic marker in human breast carcinoma

Evans

Rowlands²,

Law³

et al. 1994

Br J Cancer

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“…In these studies, the tissue concentrations of E 1 and E 2 were generally several times higher than those detected in the plasma or in the area of the normal breast tissues of the same postmenopausal patients, despite markedly low levels of circulating estrogens. In contrast to breast carcinoma cases, there is limited data regarding tissue estrogen concentrations in endometrial carcinoma tissues (Bonney et al 1986, Vermeulen-Meiners et al 1986, Naitoh et al 1989, Berstein et al 2003. Berstein and coworkers examined 78 endometrial carcinomas and detected higher concentrations of E 2 in carcinoma tissue specimens compared with macroscopically normal endometrium (Berstein et al 2003).…”

Section: Intracrinologymentioning

confidence: 99%

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Itō¹,

Miki²,

Suzuki³

et al. 2016

Endocrine-Related Cancer

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In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated.

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Estrone sulfate and sulfatase activity in human breast cancer and endometrial cancer

Cited by 70 publications

References 26 publications

Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction

Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction

Intratumoral oestrone sulphatase activity as a prognostic marker in human breast carcinoma

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

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