The local hormonal environment and related biomarkers in the normal breast

Khan, Seema A.; Bhandare, Deepa; Chatterton, Robert T.

doi:10.1677/erc.1.00732

Cited by 21 publications

(9 citation statements)

References 79 publications

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“…ER and PR expression in breast epithelial cells is considered a marker for risk of developing breast cancer and for preventive intervention (41)(42)(43); HER-2 is a prognostic marker (44)(45)(46). Therefore, in this study, we have evaluated the expression of ER, PR, and HER-2 in adjacent nonneoplastic canine mammary tissue, IELs, and tumors by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Mammary Intraepithelial Lesions in Dogs—A Model of Breast Cancer

Antuofermo¹,

Miller²,

Pirino

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Mammary intraepithelial lesions (IEL) are nowadays frequently diagnosed as a result of the success of mammographic screening, education programs, and awareness by women. Establishment of an animal model for these lesions to test treatment or preventive modalities is a prerequisite for human clinical trials. A model for spontaneous IELs, especially for estrogen receptor (ER)-negative lesions, does not exist. This study describes the histologic and immunohistochemical similarity between human and canine mammary IELs. Mammary tumors from 200 dogs were classified and histologic sections of the excisional specimens were evaluated for IELs. IELs, found in specimens from 60 dogs, were categorized as adenosis, sclerosing adenosis, intraductal papilloma, sclerosing papilloma, ductal hyperplasia, atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS; high, intermediate, and low grade). Most proliferative IELs without atypia were associated with benign tumors, whereas IELs with atypia (ADH and DCIS) were generally associated with mammary cancer. ER-A expression was significantly low or absent in most ADH and DCIS lesions as well as in their associated tumors. Ki67 expression was significantly higher in high-grade DCIS than in hyperplasia or low-grade DCIS. Two thirds of high-grade DCIS lesions were positive for HER-2. Canine mammary IELs were strikingly similar to those of the human breast. The frequency of IELs in the dog, their association with spontaneous mammary cancer, their pattern of ER-A and HER-2 expression, and their histologic resemblance to human IELs may make the dog an ideal model to study human ER-negative (both HER-2 positive and negative) breast cancer progression as well as prevention and treatment. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2247 -56)

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Section: Discussionmentioning

confidence: 99%

Spontaneous Mammary Intraepithelial Lesions in Dogs—A Model of Breast Cancer

Antuofermo¹,

Miller²,

Pirino

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…This assumption is underlined by the observation of very high concentrations in the cord blood (mean concentration: 750 nM, ranging from 240 to 1670 nM) (Baik et al, 2005) and the presence of elevated progesterone levels in nipple aspiration fluid of human breast (approximately 300 nM) (Khan et al, 2005).…”

Section: Oatp2b1-mediated Steroid Uptakementioning

confidence: 99%

Modification of OATP2B1-Mediated Transport by Steroid Hormones

Grube¹,

Köck²,

Karner³

et al. 2006

Mol Pharmacol

103

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The family of the organic anion transporting polypeptides forms an increasing group of uptake transport proteins with a wide substrate spectrum. Although the expression of some members of this group, such as organic anion transporting polypeptide (OATP)-A or C, is limited to special tissues (such as liver or brain), the organic anion transporting polypeptide 2B1 (OATP-B/SLCO2B1) is expressed in many organs, including liver, placenta, mammary gland, brain, and intestine. However, little is known about its function in those tissues because only a limited number of compounds, such as dehydroepiandrosterone-sulfate (DHEAS) and estrone-3-sulfate (E3S), have been characterized as OATP2B1 substrates. To further elucidate the role of OATP2B1 on steroid transport, we examined the influence of steroid hormones on OATP2B1-mediated E3S and DHEAS uptake using OATP2B1-overexpressing Madin-Darby canine kidney II cells. We identified unconjugated androgens (e.g., testosterone) as potent inhibitors for OATP2B1. In contrast, gestagenes such as progesterone enhanced E3S uptake in a concentration-dependent manner to up to 300% of the control, accompanied by a significant decrease in the OATP2B1 K m value for E3S (control, K m ϭ 14 M; in the presence of 31.6 M progesterone, K m ϭ 3.6 M). Moreover, we demonstrated that testosterone and progesterone are not substrates of OATP2B1, indicating an allosteric mechanism for the observed effects. Furthermore, we showed that progesterone enhances the OATP2B1-dependent pregnenolone sulfate transport. Taken together, the results indicate functional modification of OATP2B1-mediated E3S and DHEAS as well as pregnenolone sulfate transport through steroid hormones such as progesterone. These effects can have physiological consequences for the organ-specific uptake of steroids.

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“…FNA is a breast epithelial sampling technology that provides a new opportunity for breast molecular studies in asymptomatic women [9,10]. As only a few cells of breast tissue samples can be obtained by FNA [7], a highly sensitive method for detecting mRNA in the breast tissue aspirates is critical.…”

Section: Discussionmentioning

confidence: 99%

Aromatase and steroid sulfatase mRNA expression in fine needle aspirates from benign and malignant breast disorders

Gao

Liu

et al. 2012

Chin. Sci. Bull.

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The fine needle aspiration (FNA) test is a convenient and tolerable technique with minimal invasion that is accepted by most women. Local estrogen synthesis depends mainly on the aromatase and steroid sulfatase pathways that are believed to play important roles in breast carcinogenesis. However, little is known about the level of aromatase and steroid sulfatase mRNA expression in FNA samples which contain only small amounts of tissue. The nested Q-PCR assay has been proven to be a highly sensitive and specific method to assess the aromatase expression of breast tissue. In this study, aromatase and steroid sulfatase mRNA expression in 74 patients with benign or malignant disorders was evaluated and compared using nested Q-PCR and non-nested Q-PCR assays. The expression levels were analyzed and correlated with clinical parameters. No difference in the aromatase expression levels between nested and non-nested Q-PCR was noticed. Age and aromatase mRNA expression level were two independent risk factors for breast cancer (P=0.04 and P=0.00, respectively), while menopausal status and steroid sulfatase mRNA expression levels were not associated with breast cancer. This study showed that both nested and non-nested Q-PCR assays were effective methods for research using FNA breast samples.aromatase, steroid sulfatase, breast disorders, fine needle aspirate, nested Q-PCR

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The local hormonal environment and related biomarkers in the normal breast

Cited by 21 publications

References 79 publications

Spontaneous Mammary Intraepithelial Lesions in Dogs—A Model of Breast Cancer

Spontaneous Mammary Intraepithelial Lesions in Dogs—A Model of Breast Cancer

Modification of OATP2B1-Mediated Transport by Steroid Hormones

Aromatase and steroid sulfatase mRNA expression in fine needle aspirates from benign and malignant breast disorders

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