Steroid Sulfatase and Estrogen Sulfotransferase in Colon Carcinoma: Regulators of Intratumoral Estrogen Concentrations and Potent Prognostic Factors

Sato, Ryuichiro; Suzuki, Takashi; Katayose, Yu; Miura, Koh; Shiiba, Kenichi; Tateno, Hiroo; Miki, Yasuhiro; Akahira, Jun Ichi; Kamogawa, Yukiko; Nagasaki, Shuji; Yamamoto, Kuniharu; Takayuki,; Egawa, Shinichi; Evans, Dean B.; Unno, Michiaki; Sasano, Hironobu

doi:10.1158/0008-5472.can-08-0906

Cited by 60 publications

(61 citation statements)

References 48 publications

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“…In our present study, the results of combined LCM and RT-PCR analysis of aromatase showed that in lung carcinoma, aromatase mRNA/protein was detected predominantly in parenchymal cells of lung cancer tissues in contrast to its localization in human breast carcinoma evaluated by the same methodology (8). Similar localization of aromatase has also been reported in colon (26), gastric (27), and oral squamous cell carcinomas (28). Aromatase immunoreactivity was also reported to be predominantly present in intratumoral stromal cells in endometrial (29,30) and prostatic (31) carcinomas as well as in breast carcinoma (9,10,13).…”

Section: Discussionsupporting

confidence: 83%

Intratumoral Localization of Aromatase and Interaction between Stromal and Parenchymal Cells in the Non–Small Cell Lung Carcinoma Microenvironment

et al. 2010

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Estrogens produced as a result of intratumoral aromatization has been recently shown to play important roles in proliferation of human non-small cell lung carcinomas (NSCLC), but the details have remained largely unknown. Therefore, in this study, we evaluated the possible roles of intratumoral aromatase in NSCLCs as follows: (a) evaluation of intratumoral localization of aromatase mRNA/protein in six lung adenocarcinoma cases using laser capture microdissection combined with quantitative reverse transcriptase-PCR and immunohistochemistry; (b) examination of the possible effects of isolated stromal cells from lung carcinoma tissues on aromatase mRNA transcript expression in lung carcinoma cell lines (A549 and LK87) through a coculture system; and (c) screening of cytokines derived from stromal LK001S and LK002S cells using cytokine antibody arrays and subsequent evaluation of effects of these cytokines on aromatase expression in A549 and LK87. Both aromatase mRNA and protein were mainly detected in intratumoral carcinoma cells but not in stromal cells. Aromatase expression of A549 and LK87 was upregulated in the presence of LK001S or LK002S cells. Several cytokines such as interleukin-6 (IL-6), oncostatin M, and tumor necrosis factor-α, all known as inducible factors of aromatase gene, were detected in conditioned media of LK001S and LK002S cells. Treatment of both oncostatin M and IL-6 induced aromatase gene expression in A549 an LK87, respectively. These results all indicated that intratumoral microenvironments, especially carcinoma-stromal cell interactions, play a pivotal role in the regulation of intratumoral estrogen synthesis through aromatase expression in human lung adenocarcinomas. Cancer Res; 70(16); 6659-69. ©2010 AACR.

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Section: Discussionsupporting

confidence: 83%

Intratumoral Localization of Aromatase and Interaction between Stromal and Parenchymal Cells in the Non–Small Cell Lung Carcinoma Microenvironment

et al. 2010

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“…For example, in human colorectal cancer cell lines, estradiol has been shown to activate the mitogenactivated protein kinase cascade, a pathway that plays a key role in the stimulation of DNA and protein synthesis, which induces cell growth and proliferation (10,11). In addition, colorectal cancer tissue was found to have higher levels of estradiol activity compared with nonmalignant colorectal tissue (34,35), and a cross-sectional study of colon cancer patients reported that colon carcinoma tissue had a statistically significant twofold higher level of total estrogen compared with normal colon mucosa (36). Low concentrations of intratumoral estrogen were also statistically significantly associated with better prognosis (36), and higher levels of estrogen receptor beta expression were reported in colorectal carcinomas compared with normal colonic mucosa (37).…”

Section: Discussionmentioning

confidence: 99%

Reproductive history and risk of colorectal cancer in postmenopausal women.

Zervoudakis¹,

Schatzkin²,

Strickler³

et al. 2010

JCO

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Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States, with approximately 142 570 new cases and 51 370 colorectal cancer-related deaths expected in 2010 (1). Observational and experimental evidence suggest that sex hormones, particularly estrogen, play a role in colorectal cancer pathogenesis (2). Most notably, a substantial body of epidemiological data supports an inverse relationship between postmenopausal oral hormone therapy use and the risk of colorectal cancer (3), an association that was confirmed by results of the Women's Health Initiative (WHI) Clinical Trial, which reported a statistically significant decreased risk of colorectal cancer among women using estrogen plus progestin formulations (but not among women using estrogen alone) compared with women using placebo (4,5).By contrast, two subsequent prospective studies reported a positive association between endogenous estrogen level and the risk of colorectal cancer in postmenopausal women. The first investigation, which was conducted in the WHI Observational Study, found that a high endogenous level of estrogen was associated with a 1.5-fold increased risk of developing colorectal cancer after adjustment for established colorectal cancer risk factors (6). Similarly, the New York University Women's Health Study reported a 60% increased risk of colorectal cancer for women in the highest quartile of circulating estrogen level compared with those in the lowest quartile (7). The positive associations between endogenous estrogen level and the risk of colorectal cancer reported by these investigations are consistent with laboratory data demonstrating the proliferative effects of exogenous estradiol in colorectal tissue and in colorectal cancer cell lines (8-11). The findings from these observational and experimental studies, when considered together with the data on hormone therapy use and colorectal cancer, suggest that endogenous and exogenous sex hormones may play different roles in colorectal tumorigenesis.

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“…Estrogens may induce colorectal cancer cell apoptosis by binding to estrogen receptor b, [73,94]. A2 2.4 fold increased of estrogen (mainly estrone rather than estradiol) were observed in colon carcinoma tissues [77]. This may be related to overexpression of enzymes involved in steroid synthesis pathway, such as sulfatase and mainly 17HSD isoform 2 [77,79].…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 98%

“…A2 2.4 fold increased of estrogen (mainly estrone rather than estradiol) were observed in colon carcinoma tissues [77]. This may be related to overexpression of enzymes involved in steroid synthesis pathway, such as sulfatase and mainly 17HSD isoform 2 [77,79]. The 17bHSD2 catalyzes the oxidative transformation of estradiol to estrone [74].…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

“…Early in vitro and in vivo studies observed the expression of enzymes involved in estrogen metabolism in colorec tal cancer cell lines and normal gut mucosa [33,73 76]. Evidence of estrogen production by the IECs in healthy humans was then assessed leading to the observation of higher mucosal production of estrone as compared to estradiol [77].…”

Section: Metabolism and Function Of Other Steroids In The Gutmentioning

confidence: 99%

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Intestinal steroidogenesis

et al. 2015

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a b s t r a c tSteroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of ste roidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor 1 (SF 1) but a closely related homolog, namely the liver receptor homolog 1 (LRH 1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel dis eases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions.

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Steroid Sulfatase and Estrogen Sulfotransferase in Colon Carcinoma: Regulators of Intratumoral Estrogen Concentrations and Potent Prognostic Factors

Cited by 60 publications

References 48 publications

Intratumoral Localization of Aromatase and Interaction between Stromal and Parenchymal Cells in the Non–Small Cell Lung Carcinoma Microenvironment

Intratumoral Localization of Aromatase and Interaction between Stromal and Parenchymal Cells in the Non–Small Cell Lung Carcinoma Microenvironment

Reproductive history and risk of colorectal cancer in postmenopausal women.

Intestinal steroidogenesis

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