Estradiol is trophic for colon cancer in mice: Effect on ornithine decarboxylase and c-myc messenger RNA

Narayan, Satya; Rajakumar, G.; Prouix, Heidi; Singh, Pomila

doi:10.1016/0016-5085(92)91441-6

Cited by 29 publications

(14 citation statements)

References 35 publications

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“…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)(9)(10)(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.…”

supporting

confidence: 76%

“…Both investigations reported statistically significant positive associations between circulating estrogen levels and the risk of colorectal cancer, and one study (6) also controlled for circulating insulin and free insulin-like growth factor I (IGF-I) levels and obesity, which suggests that the relationship between estrogen and risk of colorectal cancer may be independent of obesity-related pathways. In vitro data also support a role for estrogen in colorectal tumorigenesis (8)(9)(10)33). 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).…”

Section: Discussionmentioning

confidence: 97%

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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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supporting

confidence: 76%

Section: Discussionmentioning

confidence: 97%

Reproductive history and risk of colorectal cancer in postmenopausal women.

Zervoudakis¹,

Schatzkin²,

Strickler³

et al. 2010

JCO

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show abstract

“…Although this observation requires confirmation in other populations, the findings are biologically plausible. Several in vitro studies have shown that estrogen may have mitogenic and possibly tumorigenic effects on colorectal cells (34)(35)(36)(37)(38)(39)(40)(41)(42). For example, in human colorectal cancer cell lines, estradiol activates the mitogen-activated protein kinase cascade, a key pathway in the stimulation of DNA and protein synthesis that can induce cell growth and proliferation (36,39).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, although several laboratory studies reported that estrogen has antitumorigenic activity in keeping with the protective effects of hormone therapy (24)(25)(26)(27)(28)(29)(30)(31)(32)(33), other studies found that estrogen has mitogenic effects on colorectal cells (34)(35)(36)(37)(38)(39)(40)(41)(42). Furthermore, oral estrogens have certain biological effects that differ from those of endogenous estrogens; most notably, oral hormone therapy exposes the liver to a large bolus of estrogen altering hepatic protein synthesis, a phenomenon known as the ''first-pass effect'' (43).…”

Section: Introductionmentioning

confidence: 99%

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

et al. 2008

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Obesity is a risk factor for colorectal cancer, and hyperinsulinemia, a common condition in obese patients, may underlie this relationship. Insulin, in addition to its metabolic effects, has promitotic and antiapoptotic activity that may be tumorigenic. Insulin-like growth factor (IGF)-I, a related hormone, shares sequence homology with insulin, and has even stronger mitogenic effects. However, few prospective colorectal cancer studies directly measured fasting insulin, and none evaluated free IGF-I, or endogenous estradiol, a potential cofactor in postmenopausal women. Therefore, we conducted a casecohort investigation of colorectal cancer among nondiabetic subjects enrolled in the Women's Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. Fasting baseline serum specimens from all incident colorectal cancer cases (n = 438) and a random subcohort (n = 816) of Women's Health Initiative Observational Study subjects were tested for insulin, glucose, total IGF-I, free IGF-I, IGF binding protein-3, and estradiol. Comparing extreme quartiles, insulin [hazard ratio (HR) q4-q1 , 1.73; 95% confidence interval (CI), 1.16-2.57; P trend = 0.005], waist circumference (HR q4-q1 , 1.82; 95% CI, 1.22-2.70; P trend = 0.001), and free IGF-I (HR q4-q1 , 1.35; 95% CI, 0.92-1.98; P trend = 0.05) were each associated with colorectal cancer incidence in multivariate models. However, these associations each became nonsignificant when adjusted for one another. Endogenous estradiol levels, in contrast, were positively associated with risk of colorectal cancer (HR comparing high versus low levels, 1.53; 95% CI, 1.05-2.22), even after control for insulin, free IGF-I, and waist circumference. These data suggest the existence of at least two independent biological pathways that are related to colorectal cancer: one that involves endogenous estradiol, and a second pathway broadly associated with obesity, hyperinsulinemia, and free IGF-I. [Cancer Res 2008;68(1):329-37]

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“…Similarly to GCs, estrogens metabolism (mainly estradiol) seems to occur predominantly in the intestinal crypts of the colon and may thereby exert a significant effect on colonic epithelial cell growth [33,80]. Of interest in this regard is the observation that ovariectomy appears to induce colonic crypt atrophy [81].…”

Section: Metabolism and Function Of Other Steroids In The Gutmentioning

confidence: 99%

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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Estradiol is trophic for colon cancer in mice: Effect on ornithine decarboxylase and c-myc messenger RNA

Cited by 29 publications

References 35 publications

Reproductive history and risk of colorectal cancer in postmenopausal women.

Reproductive history and risk of colorectal cancer in postmenopausal women.

Insulin, Insulin-like Growth Factor-I, Endogenous Estradiol, and Risk of Colorectal Cancer in Postmenopausal Women

Intestinal steroidogenesis

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