Urinary Cadmium and Serum Levels of Estrogens and Androgens in Postmenopausal Japanese Women

Nagata, Chisato; Nagao, Yasuko; Shibuya, Chiken; Kashiki, Yoshitomo; Shimizu, Hiroyuki

doi:10.1158/1055-9965.epi-04-0619

Cited by 78 publications

(62 citation statements)

References 23 publications

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“…Other metals, such as arsenic and uranium have also been evaluated for the reproductive tissue effects, but Cd is the only one with demonstrated effects on mammary proliferation (Johnson et al, 2003;Fenton, 2006). Although there is no definitive epidemiological evidence showing a positive relationship between Cd exposure and breast cancer incidence in the general population (Nagata et al, 2005;McElroy et al, 2006), as a xenoestrogen, Cd may play a role in cancer promotion and progression after the cancer is initiated (Brody and Rudel, 2003;Yager and Davidson, 2006). The mechanism by which Cd disrupts endocrine function remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium

Liu

Shaikh

2008

Toxicology and Applied Pharmacology

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Cadmium (Cd), an endocrine disruptor, can induce a variety of signaling events including the activation of ERK1/2 and AKT. In this study, the involvement of estrogen receptors (ER) in these events was evaluated in three human breast caner cell lines, MCF-7, MDA-MB-231, and SK-BR-3. The Cd-induced signal activation patterns in the three cell lines mimicked those exhibited in response to 17β-estradiol. Specifically, treatment of MCF-7 cells, that express ERα, ERβ and GPR30, to 0.5-10 μM Cd for as little as 2.5 min resulted in transient phosphorylation of ERK1/2. Cd also triggered a gradual increase and sustained activation of AKT during the 60 min treatment period. In SK-BR-3 cells, that express only GPR30, Cd also caused a transient activation of ERK1/2, but not of AKT. In contrast, in MDA-MB-231 cells that express only ERβ, Cd was unable to cause rapid activation of either ERK1/2 or AKT. A transient phosphorylation of ERα was also observed within 2.5 min of Cd exposure in the MCF-7 cells. While the estrogen receptor antagonist, ICI 182,780, did not prevent the effect of Cd on these signals, specific siRNA against hERα significantly reduced Cd-induced activation of ERK1/2 and completely blocked the activation of AKT. It is concluded that Cd, like estradiol, can cause rapid activation of ERK1/2 and AKT and that these signaling events are mediated by possible interaction with membrane ERα and GPR30, but not ERβ.

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Section: Discussionmentioning

confidence: 99%

Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium

Liu

Shaikh

2008

Toxicology and Applied Pharmacology

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“…Municipal letters inviting to the screening were mailed to women residing in the surrounding areas. Details of the study have been described elsewhere (13). The main purpose of the study was to identify the determinants of mammographic breast density.…”

Section: Methodsmentioning

confidence: 99%

Light Exposure at Night, Urinary 6-Sulfatoxymelatonin, and Serum Estrogens and Androgens in Postmenopausal Japanese Women

Nagata

Nagao

Yamamoto

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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It has been hypothesized that exposure to light at night increases the risk of breast cancer by suppressing the normal nocturnal increase in melatonin production and release, thereby resulting in increased levels of circulating estrogen. We assessed associations among concentrations of serum estrogen and androgen and the principal metabolite of melatonin in urine, 6-sulfatoxymelatonin, and exposure to light at night based on information regarding the sleeping habits and history of graveyard-shift work of 206 postmenopausal Japanese women. Serum estradiol level was significantly higher in women who were not asleep at or after 1:00 a.m. (the approximate time of the melatonin peak) than those who were asleep after controlling for covariates. Significantly increased estrone levels were observed in women who had worked graveyard shift. Serum testosterone and DHEA sulfate were unrelated to sleeping habits and history of graveyard-shift work. Urinary 6-sulfatoxymelatonin was lower in women who were not asleep at or after 1:00 a.m. on weekends than those who were asleep at this time, but the difference was of borderline significance (P = 0.08). There was no significant association between urinary 6-sulfatoxymelatonin and any serum hormone levels. These data suggest that exposure to light at night has implications for the risk of breast cancer in postmenopausal women. However, the potential role of melatonin as an intervening factor between light exposure at night and the serum concentrations of estrogen was equivocal. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1418 -23)

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“…Cadmium-cancer associations are listed in Table 1 in chronological order. In a hospital-based study on 165 postmenopausal Japanese women, mean age 59 yrs, Nagata et al (2005) observed a 28% increase in serum testosterone (a breast cancer risk factor) among those with urinary cadmium ≥ 3 µg/g creatinine. Nawrot et al (2006) observed a 1.7-fold rise in lung cancer risk among those with a two-fold increase in cadmium body burden.…”

Section: Metallothionein Sequestration and Cadmium's Long Half-lifementioning

confidence: 99%

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

Satarug

2012

Tohoku J. Exp. Med.

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Many decades after an outbreak of severe cadmium poisoning, known as Itai-itai disease, cadmium continues to pose a significant threat to human health worldwide. This review provides an update on the effects of this environmental toxicant cadmium, observed in numerous populations despite modest exposure levels. In addition, it describes the current knowledge on the link between heme catabolism and glycolysis. It examines novel functions of heme oxygenase-2 (HO-2) that protect against type 2-diabetes and obesity, which have emerged from diabetic/obese phenotypes of the HO-2 knockout mouse model. Increased cancer susceptibility in type-2 diabetes has been noted in several large cohorts. This is a cause for concern, given the high prevalence of type-2 diabetes worldwide. A lifetime exposure to cadmium is associated with pre-diabetes, diabetes, and overall cancer mortality with sex-related differences in specific types of cancer. Liver and kidney are target organs for the toxic effects of cadmium. These two organs are central to the maintenance of blood glucose levels. Further, inhibition of gluconeogenesis is a known effect of heme, while cadmium has the propensity to alter heme catabolism. This raises the possibility that cadmium may mimic certain HO-2 deficiency conditions, resulting in diabetic symptoms. Intriguingly, evidence has emerged from a recent study to suggest the potential interaction and co-regulation of HO-2 with the key regulator of glycolysis: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4). HO-2 could thus be critical to a metabolic switch to cancer-prone cells because the enzyme PFKFB and glycolysis are metabolic requirements for cell proliferation and resistance to apoptosis.

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Urinary Cadmium and Serum Levels of Estrogens and Androgens in Postmenopausal Japanese Women

Cited by 78 publications

References 23 publications

Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium

Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium

Light Exposure at Night, Urinary 6-Sulfatoxymelatonin, and Serum Estrogens and Androgens in Postmenopausal Japanese Women

Emerging Roles of Cadmium and Heme Oxygenase in Type-2 Diabetes and Cancer Susceptibility

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