Aromatase activity in breast adipose tissue from women with benign and malignant breast diseases

O’Neill, John S.; Miller, William R.

doi:10.1038/bjc.1987.248

Cited by 62 publications

(31 citation statements)

References 16 publications

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“…Biochemical P450arom activity has been demonstrated in various human tissues (10,12,(23)(24)(25). However, in normal cycling human ovary, biochemical P450arom activity has been reported only by i ?…”

Section: Discussionmentioning

confidence: 99%

Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity.

Suzuki¹,

Sasano²,

Sasaki³

et al. 1994

J Histochem Cytochem.

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(3A3232).To understand changes associated with the menstrual cycle in the human ovary, it is very important to examine chronological changes in P450 aromatase (P45Oarom) enzymatic activity in the normal cycling ovary. Therefore, we initially examined the correlation between intensity of P450arom immunoreactivity and its biochemical enzymatic activity in five estrogen-producing human cancer cell lines (HHUA, Ishikawa, HEC-59, OMC-2, and MCF-7). P450arom immunointensity per cell was evaluated by the CAS 200 computed image analysis system, and its catalytic activity per lo6 culture cells was analyzed by the tritiated water method. A significant correlation (r = 0.959) was demonstrated between P450arom immunoreactivity and enzymatic activity under optimal conditions of tissue ftation and immunohistochemical procedures. We then investigated P450arom immunointensity in 31 specimens of normal cycling human ovaries to examine chronological changes in P450arom activity per cell throughout the menstrual cycle. In the follic-

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Section: Discussionmentioning

confidence: 99%

Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity.

Suzuki¹,

Sasano²,

Sasaki³

et al. 1994

J Histochem Cytochem.

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“…6). (29,30) Since growth factors such as EGF and IGF-1 also activate ER via phosphorylation, the stromal fibroblasts in breast cancer cells regulate ER activity via both estrogen-dependent and -independent pathways. (31)(32)(33)(34) To visualize and quantify the ER-activating ability of stromal fibroblasts for individual breast cancers, we established an MCF-7 clone reporting ER activity via the expression of GFP, as Fig.…”

Section: Estrogen Signaling In the Cancer Microenvironmentmentioning

confidence: 99%

Estrogen signaling pathway and its imaging in human breast cancer

2009

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Recent remarkable progress in hormonal therapy has provided great benefit to breast cancer patients, but it also evokes novel issues: how accurately can the efficacy of each hormonal therapy be predicted and how can hormonal therapy-resistant patients be treated? These clinically important issues must be closely related to the biological events in each cancer, such as the alteration of intracellular multiple estrogen signaling pathways and the estrogen-related cancer microenvironment, which has recently revealed by molecular biological studies on estrogen and its receptors. However, the estrogen signaling status in individual breast cancers has not been clarified yet. Here we present the context of these issues and introduce our study of new tools which enable the visualization of estrogen signals in individual cancers. The assessment of estrogen receptor (ER)-a activity in individual cancers or ER-activating ability of the cancer microenvironment in each breast cancer patient revealed several new findings and interesting observations. We hope that these approaches provide new clues about the estrogen-dependent mechanisms of breast cancer development, and will be useful to advance the diagnosis and treatment of breast cancer patients. (Cancer Sci 2009; 100: 1773-1778) Estrogen receptor and hormonal therapy in breast cancer E strogen controls various physiological functions in many target tissues, and is also involved in diseases such as breast cancer, endometrial cancer, vascular disease, osteoporosis, and others. In particular, breast cancer is well recognized to be a crucial tumor in which estrogen and its receptor (ER) regulate development and progression in most cases, and are therefore the most important and effective targets for the therapy of breast cancer.(1) In this article, ER refers to estrogen receptor α unless specified.The efficacy of hormonal therapies targeting estrogen and ER has been established in numerous clinical trials. Current hormonal therapies are performed by two main strategies: inhibition of ER functions by anti-estrogens and deprivation of estrogen production by luteinizing hormone-releasing hormone agonist (pre-menopause) or aromatase inhibitor (post-menopause). Prediction of the efficiency of these therapies has involved using classical molecular biomarkers such as ERα and progesterone receptor.(2) However, approximately one-third of ER-positive patients do not respond to endocrine therapy, while some ER-negative patients are responsive.(3) These discrepancies could result from different estrogenrelated intracellular signaling pathways in breast cancer cells.One of the approaches to analyze the estrogen signaling status in breast cancer is expression profiling of estrogen-regulated genes in cancer cells. Comprehensive gene expression analysis, such as DNA microarray, may be a useful tool to address this issue. So far, we have analyzed estrogen-responsive gene expression profiles among ER-positive cancer cells using comprehensive DNA microarray (4) and, based on the obtained informa...

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“…Estrogen levels in the breast cancer tissue of postmenopausal women are f10-fold higher than those in the plasma or in normal breast tissue (1,3). Aromatase is a key enzyme that catalyzes the conversion of androgen to estrogen, and its levels in breast cancer tissue were significantly higher than those in benign breast lesions (4)(5)(6). It may be responsible for the increased local estrogen production, which in turn contributes to the estrogen-sensitive proliferation of breast cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Tumor-Stromal Interaction through the Estrogen-Signaling Pathway in Human Breast Cancer

et al. 2005

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In postmenopausal breast cancers, locally produced estrogen by adipose stromal cells causes the progression of tumor growth. Although aromatase, a key enzyme of estrogen synthesis, is highly expressed in the adipose stromal cells, and aromatase inhibitors show greater efficacy in postmenopausal breast cancers, the mechanism of increasing aromatase activity in the stromal cells remains unclear. To analyze the estrogen signals and to detect the estrogen receptor (ER)-activating ability of adipose stromal cells for individual human breast cancers, we developed a new reporter cell system. To visualize the activation of ER, we first established a stable transformant, named E10, of human breast cancer MCF-7 cells by transfection with the estrogen-responsive element-green fluorescent protein (GFP) gene. E10 cells specifically express GFP when ER is activated by estrogen or by coculture with adipose stromal cells isolated from breast tumor tissues in the presence of testosterone, a substrate for aromatase. Treatment of adipose stromal cells with dexamethasone, a stimulator of aromatase gene expression, resulted in an increase in the expression of GFP in E10 cells in the coculture. Using this system, we characterized the adipose stromal cells of 67 human breast cancers and found that GFP expression levels vary among the cases, suggesting that the ability of adipose stromal cells to activate ERs is unique for individual breast cancers. High induction levels of GFP were observed more frequently in postmenopausal cases than in premenopausal cases, whereas they did not significantly correlate with the ER expression status. Aromatase inhibitors inhibited the induction of GFP expression in the coculture, but the sensitivities to the drugs varied among the individual cases. Aromatase gene expression levels in adipose stromal cells did not always correlate with their ability to induce GFP. These results suggest that this system to detect total ER activation based on the interaction with adipose stromal cells is a useful tool for analyzing local estrogen signals and for tumor-stromal interactions. (Cancer Res 2005; 65(11): 4653-62)

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Aromatase activity in breast adipose tissue from women with benign and malignant breast diseases

Cited by 62 publications

References 16 publications

Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity.

Quantitation of P450 aromatase immunoreactivity in human ovary during the menstrual cycle: relationship between the enzyme activity and immunointensity.

Estrogen signaling pathway and its imaging in human breast cancer

Tumor-Stromal Interaction through the Estrogen-Signaling Pathway in Human Breast Cancer

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