The Multisystemic Effect of Oestradiol Variations

Ovarian hormones are: oestrogenic hormone, also known as follicular hormone or female sexual hormone or chemically oestradiol; yellow body hormone, progestin or, chemically, progesterone. Oestrogenic hormone is particularly involved in the first part of the oestrus period, and the yellow body hormone in the second part (pseudo-pregnancy) and in the gestation state; the third ovarian hormone, known as relaxin, was isolated from the yellow body. Oestrogens are responsible for the development of female secondary features. Together with progesterone it controls the most important female reproductive processes. The most biologically active of oestrogens is 17b-oestradiol. Oestradiol is produced by ovarian follicles, testicles, but also by some organs such as the liver, adrenal glands, mammary glands and the brain. Oestradiol activates two specific nuclear proteins, oestrogen receptors alpha (ER�) and oestrogen receptors beta (Er�). Oestrogen receptors alpha are predominant in the mammary gland, genital apparatus, bone, nervous and cardiovascular system. Oestrogen receptors beta are found in the uterus, monocytes, tissue macrophages, colon and lung epithelial cells, epithelial cells of the prostate. The main actions of oestradiol are: endometrial proliferation, effects on the vagina and the mammary gland; it also has a role in preventing osteoporosis and reducing cardiovascular risk. Oestradiol is primarily produced in the ovary (the follicle, yellow body), but small amounts are also formed in the testicles and the cortex of the adrenals. In pregnancy, oestrogen is mainly produced by the placenta. Approximately 98% of oestradiol is linked to sex hormone binding globulin (SHBG). The level of oestradiol increases throughout the follicular phase of the menstrual cycle in close dependence with the growth and development of the ovarian follicle. For the determination of oestradiol, we conducted a study of 64 people, of which 47 women (73.43% and 17 men (26.57%). The presence of oestrogen receptors alpha indicates an increased risk of breast cancer. Breast cancer is hormone dependent, 74% of cases are oestrogen-positive receptors, and 30% of cases are progesterone-positive receptors. The main reason for the development of hyperplasia is the increase in oestrogen levels.

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Mammary gland adipocytes in lactation cycle, obesity and breast cancer

Reviews in Endocrine and Metabolic Disorders ◽

10.1007/s11154-021-09633-5 ◽

2021 ◽

Author(s):

Georgia Colleluori ◽

Jessica Perugini ◽

Giorgio Barbatelli ◽

Saverio Cinti

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Epithelial Cells ◽

Close Association ◽

Critical Role ◽

Exocrine Gland ◽

Plastic Properties ◽

Lactation Cycle ◽

Gland Development

AbstractThe mammary gland (MG) is an exocrine gland present in female mammals responsible for the production and secretion of milk during the process of lactation. It is mainly composed by epithelial cells and adipocytes. Among the features that make the MG unique there are 1) its highly plastic properties displayed during pregnancy, lactation and involution (all steps belonging to the lactation cycle) and 2) its requirement to grow in close association with adipocytes which are absolutely necessary to ensure MG’s proper development at puberty and remodeling during the lactation cycle. Although MG adipocytes play such a critical role for the gland development, most of the studies have focused on its epithelial component only, leaving the role of the neighboring adipocytes largely unexplored. In this review we aim to describe evidences regarding MG’s adipocytes role and properties in physiologic conditions (gland development and lactation cycle), obesity and breast cancer, emphasizing the existing gaps in the literature which deserve further investigation.

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EphB6 Regulates TFEB-Lysosomal Pathway and Survival of Disseminated Indolent Breast Cancer Cells

Cancers ◽

10.3390/cancers13051079 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1079

Author(s):

Manuela Zangrossi ◽

Patrizia Romani ◽

Probir Chakravarty ◽

Colin D.H. Ratcliffe ◽

Steven Hooper ◽

...

Keyword(s):

Breast Cancer ◽

Epithelial Cells ◽

Cancer Cells ◽

Lung Epithelial Cells ◽

Late Relapse ◽

Alveolar Type ◽

Type I ◽

Extrinsic Factors ◽

Lung Epithelial

Late relapse of disseminated cancer cells is a common feature of breast and prostate tumors. Several intrinsic and extrinsic factors have been shown to affect quiescence and reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining the survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes survival of DDCCs of estrogen receptor-positive (ER+) breast tumors. By using a lung organotypic system and in vivo dissemination assays, here we show that the TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct coculture of DDCCs with alveolar type I-like lung epithelial cells and dissemination in the lung drive lysosomal accumulation and EphB6 induction. EphB6 contributes to survival, TFEB transcriptional activity, and lysosome formation in DDCCs in vitro and in vivo. Furthermore, signaling from EphB6 promotes the proliferation of surrounding lung parenchymal cells in vivo. Our data provide evidence that EphB6 is a key factor in the crosstalk between disseminated dormant cancer cells and the lung parenchyma and that the TFEB-lysosomal pathway plays an important role in the persistence of DDCCs.

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Abstract LB-443: Methylation in exfoliated epithelial cells from lactating women at increased risk for developing breast cancer

10.1158/1538-7445.am2011-lb-443 ◽

2011 ◽

Author(s):

Eva P. Browne ◽

Elizabeth C. Punska ◽

Douglas L. Anderton ◽

Sarah Lenington ◽

Kathleen F. Arcaro

Keyword(s):

Breast Cancer ◽

Epithelial Cells ◽

Lactating Women ◽

Increased Risk

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Estrogen receptor signaling is reprogrammed during breast tumorigenesis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1819155116 ◽

2019 ◽

Vol 116 (23) ◽

pp. 11437-11443 ◽

Cited By ~ 9

Author(s):

David Chi ◽

Hari Singhal ◽

Lewyn Li ◽

Tengfei Xiao ◽

Weihan Liu ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Mammary Gland ◽

Epithelial Cells ◽

Breast Tumors ◽

Normal Mammary Gland ◽

Breast Tumorigenesis ◽

Effective Prevention ◽

Significant Difference ◽

Estrogen Stimulation

Limited knowledge of the changes in estrogen receptor (ER) signaling during the transformation of the normal mammary gland to breast cancer hinders the development of effective prevention and treatment strategies. Differences in estrogen signaling between normal human primary breast epithelial cells and primary breast tumors obtained immediately following surgical excision were explored. Transcriptional profiling of normal ER+ mature luminal mammary epithelial cells and ER+ breast tumors revealed significant difference in the response to estrogen stimulation. Consistent with these differences in gene expression, the normal and tumor ER cistromes were distinct and sufficient to segregate normal breast tissues from breast tumors. The selective enrichment of the DNA binding motif GRHL2 in the breast cancer-specific ER cistrome suggests that it may play a role in the differential function of ER in breast cancer. Depletion of GRHL2 resulted in altered ER binding and differential transcriptional responses to estrogen stimulation. Furthermore, GRHL2 was demonstrated to be essential for estrogen-stimulated proliferation of ER+ breast cancer cells. DLC1 was also identified as an estrogen-induced tumor suppressor in the normal mammary gland with decreased expression in breast cancer. In clinical cohorts, loss of DLC1 and gain of GRHL2 expression are associated with ER+ breast cancer and are independently predictive for worse survival. This study suggests that normal ER signaling is lost and tumor-specific ER signaling is gained during breast tumorigenesis. Unraveling these changes in ER signaling during breast cancer progression should aid the development of more effective prevention strategies and targeted therapeutics.

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PREDICTORS AND PREMORBID CONDITIONS OF THE DEVELOPMENT OF FEMALE GENITAL CANCER, IN PARTICULAR ENDOMETRY CANCER AND BREAST CANCER

Клінічна та профілактична медицина ◽

10.31612/2616-4868.3(17).2021.09 ◽

2021 ◽

Vol 3 (17) ◽

pp. 75-83

Author(s):

A. Petruk ◽

O. Lytvak ◽

A. Khabrat

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Amino Acids ◽

Tissue Growth ◽

Biologically Active ◽

Genital Cancer ◽

Increased Risk ◽

Risk Of Cancer ◽

Female Genital

Objective: to review a new potential diagnostic criteria for predictors and premorbid conditions of female genital cancer, including endometrial cancer and breast cancer. Materials and methods. Bibliographic, information-analytical methods were used in the work. Sources of information were data from the scientific literature on the topic of the study, modern gadleins, a review of randomized controlled trials. Results. The results of epidemiological studies suggest that the increased risk of cancer of the female reproductive system is the presence of obesity and type 2 diabetes. Potential mechanisms of their association are hyperinsulinemia, hyperglycemia, chronic inflammation, and insulin resistance. Because insulin is a major regulator of cell metabolism and is a tissue growth factor, hyperinsulinemia increases the risk of cancer. Hyperinsulinemia is associated with increased secretion of androgens by the ovaries and decreased levels of the protein that binds sex hormones, leading to higher concentrations of biologically active estrogens, which are also known to be risk factors for female genital cancer. In recent years, PFAA profiles have been found to be significantly altered in cancer and type 2 diabetes. Because cancer cells require certain amino acids to synthesize DNA, tumor growth factors, build new blood vessels, and duplicate all of their protein content, changes in PFAA profiles can be used as biomarkers of disease and different types of cancer at different stages. Conclusions. With the growing incidence of cancer, the issue of early diagnosis and detection of cancer in the pre-clinical stages remains relevant. Protein metabolism in cancer remains unclear and requires further research using a larger sample size. In addition, the biological mechanisms by which amino acids may contribute to the risk and progression of cancer or other premorbid conditions need to be elucidated. Determining the exact mechanism underlying changes in PFAA profiles has great potential for cancer diagnosis and treatment.

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EphB6 regulates TFEB-lysosomal pathway and survival of disseminated quiescent breast cancer cells

10.1101/2020.11.10.376186 ◽

2020 ◽

Author(s):

Manuela Zangrossi ◽

Probir Chakravarty ◽

Patrizia Romani ◽

Colin D.H. Ratcliffe ◽

Steven Hooper ◽

...

Keyword(s):

Breast Cancer ◽

Epithelial Cells ◽

Cancer Cells ◽

Lung Epithelial Cells ◽

Late Relapse ◽

Alveolar Type ◽

Type I ◽

Extrinsic Factors ◽

Lung Epithelial

AbstractLate relapse of disseminated cancer cells is a common feature of some types of tumors. Several intrinsic and extrinsic factors have been shown to affect reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes persistence of DDCCs from estrogen receptor positive (ER+) breast tumors. Here we show that TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct contact of DDCCs with alveolar type I-like lung epithelial cells drives lysosomal accumulation and EphB6 induction. EphB6 contributes to TFEB transcriptional activity and lysosome formation in DDCCs in vitro and in vivo, and supports survival of DDCCs in coculture and in vivo. Furthermore, signaling from EphB6 promotes the proliferative response of surrounding lung parenchymal cells in vivo.

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PO-333 Somatic engineering of mammary gland epithelial cells using CRISPR/Cas9 for rapid testing of breast cancer susceptibility genes in mouse models

10.1136/esmoopen-2018-eacr25.363 ◽

2018 ◽

Author(s):

E Pulver ◽

AC Moisés da Silva ◽

P Bouwman ◽

S Annunziato ◽

J Jonkers

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Epithelial Cells ◽

Mouse Models ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Rapid Testing ◽

Cancer Susceptibility Genes ◽

Breast Cancer Susceptibility Genes ◽

Mammary Gland Epithelial Cells

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Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination

Nature Cell Biology ◽

10.1038/s41556-020-0474-3 ◽

2020 ◽

Vol 22 (3) ◽

pp. 289-296 ◽

Cited By ~ 11

Author(s):

Marco Montagner ◽

Rahul Bhome ◽

Steven Hooper ◽

Probir Chakravarty ◽

Xiao Qin ◽

...

Keyword(s):

Breast Cancer ◽

Epithelial Cells ◽

Lung Epithelial Cells ◽

Lung Epithelial ◽

Cancer Dissemination

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The genome-wide transcriptional response to neonatal hyperoxia identifies Ahr as a key regulator

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00200.2014 ◽

2014 ◽

Vol 307 (7) ◽

pp. L516-L523 ◽

Cited By ~ 23

Author(s):

Soumyaroop Bhattacharya ◽

Zhongyang Zhou ◽

Min Yee ◽

Chin-Yi Chu ◽

Ashley M. Lopez ◽

...

Keyword(s):

Epithelial Cells ◽

High Throughput Sequencing ◽

Expression Patterns ◽

Supplemental Oxygen ◽

Lung Epithelial Cells ◽

Mouse Lung ◽

Genome Wide ◽

Increased Risk ◽

Lung Epithelial ◽

Neonatal Hyperoxia

Premature infants requiring supplemental oxygen are at increased risk for developing bronchopulmonary dysplasia (BPD). Rodent models involving neonatal exposure to excessive oxygen concentrations (hyperoxia) have helped to identify mechanisms of BPD-associated pathology. Genome-wide assessments of the effects of hyperoxia in neonatal mouse lungs could identify novel BPD-related genes and pathways. Newborn C57BL/6 mice were exposed to 100% oxygen for 10 days, and whole lung tissue RNA was used for high-throughput, sequencing-based transcriptomic analysis (RNA-Seq). Significance Analysis of Microarrays and Ingenuity Pathway Analysis were used to identify genes and pathways affected. Expression patterns for selected genes were validated by qPCR. Mechanistic relationships between genes were further tested in cultured mouse lung epithelial cells. We identified 300 genes significantly and substantially affected following acute neonatal hyperoxia. Canonical pathways dysregulated in hyperoxia lungs included nuclear fctor (erythryoid-derived-2)-like 2-mediated oxidative stress signaling, p53 signaling, eNOS signaling, and aryl hydrocarbon receptor (Ahr) pathways. Cluster analysis identified Ccnd1, Cdkn1a, and Ahr as critical regulatory nodes in the response to hyperoxia, with Ahr serving as the major effector node. A mechanistic role for Ahr was assessed in lung epithelial cells, and we confirmed its ability to regulate the expression of multiple hyperoxia markers, including Cdkn1a, Pdgfrb, and A2m. We conclude that a global assessment of gene regulation in the acute neonatal hyperoxia model of BPD-like pathology has identified Ahr as one driver of gene dysregulation.

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