The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

Alyusuf, Raja; Wazir, Javed F.; Brahmi, Urmil Prabha; Fakhro, Abdul Rahman E; Bakhiet, Moiz

doi:10.1155/2017/1403054

Cited by 7 publications

(5 citation statements)

References 34 publications

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“…However, breast cancer was one of the types of cancer not showing any difference between HSD11B1/2 expression between cancer and matched normal epithelial tissues, which suggest a paracrine, possibly by adjacent adipose tissue, instead of an autocrine effect by cortisol ( 54 ). In the same order of ideas, immunohistochemistry of 11β-HSD1 showed a presence of the enzyme in 64% of breast tumors and 97% of matched adjacent tissue ( 56 ) and GR protein amount was higher in breast tumor than in normal epithelial tissue ( 57 ). Increases in GC, particularly cortisol, can induce aromatase expression via the GRE on exon I.4 ( 26 ).…”

Section: Discussionmentioning

confidence: 74%

Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features

Laforest

Pelletier

Denver

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Adipose tissue is an important site for extragonadal steroid hormone biosynthesis through the expression and activity of P450 aromatase, 11β-hydroxysteroid dehydrogenase (HSD) 1, and 17β-HSDs. The contribution of steroid hormones produced by adjacent adipose tissue for the progression and survival of breast tumors is unknown. Objective To quantify estrogens (estradiol, estrone) and glucocorticoids (cortisol, cortisone) in breast adipose tissue from both healthy and diseased women and their relationships with adiposity indices and breast cancer prognostic markers. Design and setting Breast adipose tissue was collected at time of surgery. Patients Pre- and postmenopausal women undergoing partial mastectomy for treatment of breast cancer (n = 17) or reduction mammoplasty (n = 6) were studied. Interventions Relative estrogen and glucocorticoid amounts were determined by liquid chromatography tandem mass spectrometry. Results The targeted steroids were reliably detected and quantified in mammary adipose tissues. Women with ER+/PR+ tumor had higher relative estradiol amount than women with ER–/PR– tumor (P < .05). The ratio of estradiol-to-estrone was higher in lean women than in women with a body mass index (BMI) ≥ 25 kg/m2 (P < .05). Mixed-model analyses showed that estradiol, cortisone, and cortisol were negatively associated with tumor size (P < .05). Relationships between glucocorticoids and tumor size remained significant after adjustment for BMI. The cortisol-to-cortisone ratio was negatively associated with tumor stage (P < .05) independently of BMI. Conclusions We reliably quantified estrogens and glucocorticoids in breast adipose tissue from healthy women and women suffering from breast cancer. Our findings suggest that smaller breast tumors are associated with higher relative amounts of estradiol and cortisol in adipose tissue.

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Section: Discussionmentioning

confidence: 74%

Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features

Laforest

Pelletier

Denver

et al. 2019

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Studies have acknowledged that full-term pregnancy decreases the risk of breast cancer [1,[11][12][13]. Due to the presence of significantly high hPL levels towards the end of gestation [2,4,6], studies have suggested that hPL contributed to this protective effect [1,14].…”

Section: Discussionmentioning

confidence: 99%

The Pattern of Expression of Human Placental Lactogen Across Normal, Lactational, and Malignant Mammary Epithelium

Alyusuf¹,

Wazir²,

Brahmi³

et al. 2023

Cureus

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The immunoexpression of human placental lactogen (hPL) in mammary epithelium is not well studied in the literature. Our overall objective was to delineate the distribution pattern of hPL across mammary epithelia of varying levels of differentiation. This is the first research to study the level of expression of hPL in human lactational change epithelium. Immunohistochemistry (IHC) for hPL was performed on archival formalinfixed paraffin-embedded tissue blocks of 97 cases. These consisted of 53 invasive ductal carcinomas, 21 lactational change cases, and 23 cases of normal mammary tissue. The results of this study show underexpression of hPL in malignant epithelium compared to normal and lactational groups individually and combined as a non-malignant group. However, a higher expression of hPL was noted in mammary carcinoma of axillary lymph node (ALN)-positive patients compared to ALN-negative cases. There was no statistically significant difference between hPL expression and tumor grade, estrogen receptors (ER), progesterone receptors (PR), or human epidermal growth factor receptor 2 (HER2) status. The comparison of the immunoexpression of hPL in malignant epithelium versus lactational change epithelium may provide the basis for future studies on the possible role of hPL in the protective mechanism of lactation tissue from carcinogenesis. Our results could be explained by the proposed mechanism in the literature, which is that breast cancer cells have a potential inhibitory effect on the translation of human chorionic somatotropin hormone (CSH) mRNA into hPL protein. Our results support the literature findings of a poorer prognostic outcome for breast malignancies when hPL is expressed but require further studies using a more comprehensive range of clinical parameters.

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“…A variety of cancer cells such as liver, breast and ovarian cancer cells express receptors for glucocorticoids from the HPA axis and catecholamines from the SNS (55)(56)(57). The overexpression of glucocorticoid receptors has been identified as a potent survival pathway in breast cancer cells, and a study revealed that glucocorticoid receptor-mediated cancer cell survival signaling was activated by the administration of synthetic glucocorticoids as a premedication in chemotherapy treatment, which could potentially attenuate the effectiveness of chemotherapy (58). EPI and NE act as the physiological agonists for β-adrenergic receptors, with EPI preferentially binding to β 2 -adrenergic receptors and NE binding with higher affinity to β 1 -adrenergic receptors (59).…”

Section: Discussionmentioning

confidence: 99%

Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage

Qian

Chen

et al. 2022

Oncol Lett

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Numerous studies have shown that the release of stress hormones resulting from repeated exposure to chronic psychological stress increases DNA damage and promotes tumorigenesis. However, the mechanisms that enable cancerous cells adapt to stress hormone-induced DNA damage and survive remain unclear. The present study aimed to investigate the impact of stress hormones on the survival of liver cancer cells and the underlying mechanism. HepG2 human liver cancer cells were treated with dexamethasone (DEX), epinephrine (EPI) and norepinephrine (NE) and subjected to the testing of DNA damage, cell survival and cell apoptosis by alkaline comet assay, CCK-8 viability assay and flow cytometry, respectively. The protein expression levels of DNA damage response factors were determined by western blotting analysis. The results revealed that treatment of HepG2 cells with DEX, EPI and NE induced DNA damage without affecting cell survival or inducing apoptosis. The protein levels of wild-type p53-induced phosphatase 1 (Wip1), a type 2C family serine/threonine phosphatase, were increased, and the dephosphorylation of DNA damage response factors, including phosphorylated (p-)ataxia-telangiectasia mutated and p-checkpoint kinase 2, occurred following treatment with DEX, EPI and NE. In addition, a cycloheximide chase assay was performed to explore the protein stability under treatment with stress hormones. Compared with vehicle-treated cells, Wip1 exhibited increased protein stability in stress hormone-treated HepG2 cells. Eventually, the depletion of Wip1 using small interfering RNA verified the role of Wip1 in the modulation of stress hormone-induced DNA damage. These findings suggest that cancerous cells likely adapt to stress hormone-induced DNA damage via Wip1 upregulation. The present study provides an insight into the underlying mechanism that links chronic psychological stress with tumor growth and progression.

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The Immunoexpression of Glucocorticoid Receptors in Breast Carcinomas, Lactational Change, and Normal Breast Epithelium and Its Possible Role in Mammary Carcinogenesis

Cited by 7 publications

References 34 publications

Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features

Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features

The Pattern of Expression of Human Placental Lactogen Across Normal, Lactational, and Malignant Mammary Epithelium

Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone‑induced DNA damage

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