scholarly journals Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lone Rønnov-Jessen ◽  
Jiyoung Kim ◽  
Nadine Goldhammer ◽  
Marie Christine Klitgaard ◽  
Martynas Smicius ◽  
...  

AbstractFull term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of the third trimester surge of hormones would change their susceptibility to growth stimulation. Hormone receptor positive, reduction mammoplasty-derived human breast epithelial progenitors were exposed to a short-term, pregnancy-level of estradiol, and their subsequent response to estradiol stimulation was analyzed. Exposure to pregnancy-level of estradiol results in subsequent lower sensitivity to estrogen-induced proliferation. Expression array and immunoblotting reveal upregulation of S100A7 and down-regulation of p27, both associated with parity and epithelial differentiation. Notably, we find that the epithelial differentiation is accompanied by upregulation of E-cadherin and down-regulation of vimentin as well as by diminished migration and more mature luminal epithelial differentiation in a mouse transplantation model. Our findings are in support of a de-sensitization mechanism for pregnancy-induced prevention against breast cancer.

2017 ◽  
Vol 39 (2) ◽  
pp. 106-111 ◽  
Author(s):  
I V Zalutskii ◽  
N Yu Lukianova ◽  
D Storchai ◽  
A P Burlaka ◽  
Yu V Shvets ◽  
...  

Aim: To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro. Materials and Methods: The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used. Results: Upon treatment with lactoferrin, the increased levels of reactive oxygen species (ROS) (p < 0.05), NO generation rate by inducible NO-synthase (p < 0.05) and the level of “free” iron (p < 0.05) were observed. Moreover, the effects of lactoferrin were more pronounced in receptor-negative MDA-MB-231 and MDA-MB-468 cells. These changes resulted in increased expression of proapoptotic Bax protein (p < 0.05), reduced expression of the antiapoptotic Bcl-2 protein (p < 0.05) and level of not-oxidized mitochondrial cardiolipin (1.4–1.7-fold, p < 0.05). This, in turn, caused an increase in the percentage of apoptotic cells (by 14–24%, p < 0.05). Cytotoxic effects of lactoferrin were accompanied by an increase in the percentage of DNA in the comet tail and blocking cell cycle at G2/M phase, especially in receptor-negative cell lines. Conclusion: The study showed that exogenous lactoferrin causes a violation of an antioxidant balance by increasing the level of ROS, “free” iron and NO generation rate, resalting in the blocking of cell cycle at G2/M-phase and apoptosis of malignant cells.


Apmis ◽  
2018 ◽  
Vol 126 (4) ◽  
pp. 303-308 ◽  
Author(s):  
Elham Maleki ◽  
Kamran Ghaedi ◽  
Kahin Shahanipoor ◽  
Zana Karimi Kurdistani

2013 ◽  
Vol 36 (6) ◽  
pp. 297 ◽  
Author(s):  
Peng Xing ◽  
Ji-Guang Li ◽  
Feng Jin ◽  
Ting-Ting Zhao ◽  
Qun Liu ◽  
...  

Purpose: Obesity has been recognized as a significant risk factor for postmenopausal breast cancer. The aim of this study is to investigate the prognostic significance of body mass index (BMI) in hormone receptor-positive, operable breast cancer. Methods: In this retrospective cohort study, 1,192 consecutive patients with curative resection of primary breast cancer were enrolled. Patients were assigned to two groups according to BMI: normal or underweight (BMI < 23.0 kg/m2) and overweight or obese (BMI ≥23.0 kg/m2). Associations among BMI and clinicopathological characteristics and prognosis of patients were assessed. Results: A high BMI was significantly (P < 0.01) correlated with age, nodal stage, ALNR, ER positivity, PR positivity and menopausal status at diagnosis. Univariate analysis revealed that BMI, pathologic T stage, nodal stage, axillary lymph node ratio (ALNR) and adjuvant radiotherapy history were significantly (P < 0.05) associated with disease-free survival and overall survival, irrespective of tumour hormone receptor status. Multivariate analysis revealed BMI as an independent prognostic factor in all cases and in hormone receptor-positive cases. Conclusion: A high BMI (≥23.0 kg/m^2) is independently associated with poor prognosis in hormone receptor-positive breast cancer.


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