scholarly journals Estrogen receptor signaling is reprogrammed during breast tumorigenesis

2019 ◽  
Vol 116 (23) ◽  
pp. 11437-11443 ◽  
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.

scholarly journals Mammary gland adipocytes in lactation cycle, obesity and breast cancer

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.

scholarly journals Expression of estrogen receptor β isoforms in normal breast epithelial cells and breast cancer: regulation by methylation

Oncogene ◽  
2003 ◽  
Vol 22 (48) ◽  
pp. 7600-7606 ◽  
Author(s):  
Chunyan Zhao ◽  
Eric W-F Lam ◽  
Andrew Sunters ◽  
Eva Enmark ◽  
Manuela Tamburo De Bella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epithelial Cells ◽  
Normal Breast ◽  
Estrogen Receptor Β ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells

scholarly journals The therapeutic effects of Physalis alkekengi hydroalcoholic extract on estrogen receptor-positive breast cancer mice model: possible role of autophagy in this therapeutic response

2020 ◽  
Vol 22 (4) ◽  
pp. 181-186
Author(s):  
Zahra Zare ◽  
Maryam Teimouri
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Body Weight ◽  
Apoptotic Cell ◽  
Breast Tumors ◽  
Effective Dosage ◽  
Control Group ◽  
Specific Gene ◽  
Therapeutic Effects ◽  
Hydroalcoholic Extract

Background and aims: Although some preclinical and clinical studies have extensively confirmed the pharmacological effects of the hydroalcoholic extract (HE) of Physalis alkekengi on several diseases, little is known about the effects of P. alkekengi HE (PAHE) on breast cancer. Therefore, this study aimed to investigate the therapeutic effect of PAHE on estrogen receptor+ breast cancer. Methods: To this end, tumors were created in mice by injecting MC4L2 cells into the sternum of the mice. Then, the animals were gavaged for 16 days at 10, 50, and 100 mg/kg daily of PAHE. In addition, the tumor growth and body weight of the mice were measured on the 16th day, and they were killed on 21st day. Finally, their tumor tissues were removed and the apoptotic cell tissue and expression of the ATG-5 gene were studied as well. The experiments were repeated three times, and the data were analyzed using SPSS software (P<0.001 and P<0.05). Results: The average body weight of the control group significantly decreased 16 days after tumor establishment (P<0.001). Further, the PAHE inhibited the growth of the breast cancer tumor in higher doses (50 & 100 mg/kg, P<0.001). Based on the results, a significant histopathological alteration was found in the breast tumors of the PAHE-treated groups compared with the control group, including the decreased level of mitotic cells the intensive level of necrotic cells and lymphocyte infiltration into the breast tumors bearing mice 21 days after PAHE administration (P=0.012). Eventually, PAHE significantly increased the mRNA level of the expression of the autophagy ATG-5 specific gene in the effective dosage-treated group (50 mg/kg, P=0.037). Conclusion: The evidence suggests that the PAHE has a suitable efficacy for the treatment of ER+ breast cancer by promoting autophagy mechanisms into these tumor types

scholarly journals Zinc Signaling in the Mammary Gland: For Better and for Worse

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1204
Author(s):  
Moumita Chakraborty ◽  
Michal Hershfinkel
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Cancer Progression ◽  
Cellular Level ◽  
Normal Mammary Gland ◽  
Dna And Rna ◽  
Dna And Rna Synthesis ◽  
Zinc Signaling ◽  
Epithelial Physiology

Zinc (Zn2+) plays an essential role in epithelial physiology. Among its many effects, most prominent is its action to accelerate cell proliferation, thereby modulating wound healing. It also mediates affects in the gastrointestinal system, in the testes, and in secretory organs, including the pancreas, salivary, and prostate glands. On the cellular level, Zn2+ is involved in protein folding, DNA, and RNA synthesis, and in the function of numerous enzymes. In the mammary gland, Zn2+ accumulation in maternal milk is essential for supporting infant growth during the neonatal period. Importantly, Zn2+ signaling also has direct roles in controlling mammary gland development or, alternatively, involution. During breast cancer progression, accumulation or redistribution of Zn2+ occurs in the mammary gland, with aberrant Zn2+ signaling observed in the malignant cells. Here, we review the current understanding of the role of in Zn2+ the mammary gland, and the proteins controlling cellular Zn2+ homeostasis and signaling, including Zn2+ transporters and the Gq-coupled Zn2+ sensing receptor, ZnR/GPR39. Significant advances in our understanding of Zn2+ signaling in the normal mammary gland as well as in the context of breast cancer provides new avenues for identification of specific targets for breast cancer therapy.

scholarly journals An Interdependence between Estrogen Receptor 1 Gene Polymorphisms and Susceptibility to Breast Cancer

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Maryam Saneipour ◽  
Abdolkarim Sheikhi ◽  
Abbas Moridnia
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Allele Frequency ◽  
Genetic Alterations ◽  
Recessive Model ◽  
Control Group ◽  
Genotype Distribution ◽  
Increased Risk ◽  
Significant Difference ◽  
Estrogen Receptor 1

Background: Breast cancer (BC) is the most common malignant tumor in women around the world. Genetic factors do play a vital role in the development and progression of BC. Genetic alterations in the ESR1 (estrogen receptor 1) gene can lead to estrogen dysfunction and increased risk for BC. Nevertheless, due to genetic diversity, the information from different studies is contradictory and controversial. Objectives: This study aimed to investigate the potential relationship between the rs1801132 and rs2234693 single nucleotide polymorphism (SNPs) of the ESR1 gene with susceptibility to BC in the Iranian population. Methods: The genotyping of the rs2234693 and rs1801132 SNPs was assessed in 63 BC patients referred to Imam Hasan Mojtaba Center, which is a charity-based foundation for cancer care in Dezful, Iran, from March 2018 to November 2019. Also, 65 healthy women were selected as a control group. The genotyping of the SNPs was performed using the high-resolution melting (HRM) technique and confirmed by DNA sequencing. Results: The genotype distribution and allele frequency of the rs2234693 SNP were significantly different in BC patients compared to the control group (genotype frequency with P = 0.018 and allele frequency with P = 0.004, OR = 2.085, 95% CI = 1.253 -3.468). In genetic models, rs2234693 increased BC risk in recessive model (P = 0.005, OR = 2.813, 95% CI = 1.363 - 5.802). However, there was no significant difference regarding genotype distribution of the rs1801132 SNP between the BC patients and controls. Conclusions: Our results showed that the CC genotype of the rs2234693 SNP is significantly associated with BC. Accordingly, it can be suggested that the rs2234693 SNP be considered for susceptibility to BC.

scholarly journals AXL Is a Driver of Stemness in Normal Mammary Gland and Breast Cancer

iScience ◽  
2020 ◽  
Vol 23 (11) ◽  
pp. 101649
Author(s):  
Agnete S.T. Engelsen ◽  
Katarzyna Wnuk-Lipinska ◽  
Sebastien Bougnaud ◽  
Fanny A. Pelissier Vatter ◽  
Crina Tiron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Normal Mammary Gland

scholarly journals Future perspectives of selective estrogen receptor modulators used alone and in combination with DHEA

2006 ◽  
Vol 13 (2) ◽  
pp. 335-355 ◽  
Author(s):  
F Labrie
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Mammary Gland ◽  
Cancer Prevention ◽  
Women’S Health ◽  
Women's Health ◽  
Aromatase Inhibitors ◽  
Estrogenic Activity ◽  
Antagonistic Activity ◽  
Breast Cancer Prevention

Breast cancer is the most frequently diagnosed and the second cause of cancer death in women, thus making breast cancer a most feared disease. Since breast cancer metastasizes early and it is unlikely that improvements in the treatment of metastatic disease could permit a cure in most cases in the foreseeable future, it is clear that prevention is essential in order practically to eliminate deaths from breast cancer. Tamoxifen is the only selective estrogen receptor modulator (SERM) currently registered for use in breast cancer prevention; the tamoxifen versus raloxifene study should indicate the efficacy of this compound compared with raloxifene. The recent benefits of aromatase inhibitors over tamoxifen indicate the advantages of a blockade of estrogens more complete than the one achieved with tamoxifen, a SERM having some estrogenic activity in the mammary gland and an even higher estrogenic action in the uterus. However, it is unlikely that the general estrogen ablation achieved with aromatase inhibitors will be acceptable for the long-term use required for prevention. It is thus important to develop SERMs with highly potent and pure antagonistic activity in the mammary gland and uterus while possessing estrogen-like activity in tissues of particular importance for women’s health, namely the bones and the cardiovascular system. However, it is expected that a SERM alone will not meet all the requirements of women’s health at the postmenopause when ovarian estrogen secretion has ceased and peripheral formation of androgens and estrogens from DHEA by intracrine mechanisms is decreased by 60% or more. One possibility is to combine a SERM with DHEA, a precursor of sex steroids that permits, somewhat like SERMs, tissue-specific formation of androgens and/or estrogens according to the level of expression of the steroidogenic and steroid-inactivating enzymes. DHEA could thus compensate for the important loss of androgens that accompanies aging and could also permit sex steroid formation and action in the brain while breast cancer prevention would be achieved by the SERM.

Apoptosis in mammary gland and cancer.

2000 ◽  
pp. 257-269 ◽  
Author(s):  
R Kumar ◽  
R K Vadlamudi ◽  
L Adam
Keyword(s):  
Breast Cancer ◽  
Mammary Gland ◽  
Mammary Gland Development ◽  
Expression Profiles ◽  
Critical Role ◽  
Physiological Mechanism ◽  
Cell Loss ◽  
Normal Mammary Gland ◽  
Organ Systems ◽  
Gland Development

Homeostasis in normal tissue is regulated by a balance between proliferative activity and cell loss by apoptosis. Apoptosis is a physiological mechanism of cell loss that depends on both pre-existing proteins and de novo protein synthesis, and the process of apoptosis is integral to normal mammary gland development and in many diseases, including breast cancer. The mammary gland is one of the few organ systems in mammals that completes its morphologic development postnatally during two discrete physiologic states, puberty and pregnancy. The susceptibility of the mammary gland to tumorigenesis is influenced by its normal development, particularly during stages of puberty and pregnancy that are characterized by marked alterations in breast cell proliferation and differentiation. Numerous epidemiologic studies have suggested that specific details in the development of the mammary gland play a critical role in breast cancer risk. Mammary gland development is characterized by dynamic changes in the expression profiles of Bcl-2 family members. The expression of Bcl-2 family proteins in breast cancer is also influenced by estradiol and by progestin. Since the ratio of proapoptotic to antiapoptotic proteins determines apoptosis or cell survival, hormone levels may have important implications in the therapeutic prevention of breast cancer.

165. LOCATION OF ACTIVE TGFB1 IN THE MAMMARY GLAND DURING DIFFERENT STAGES OF DEVELOPMENT

2010 ◽  
Vol 22 (9) ◽  
pp. 83
Author(s):  
X. Sun ◽  
S. A. Robertson ◽  
W. V. Ingman
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Developmental Stage ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biological Effects ◽  
In Situ Hybridisation ◽  
Late Pregnancy ◽  
Qualitative Assessment ◽  
Normal Mammary Gland

Development of the mammary gland involves complex interactions between epithelial and stromal cells under the influence of hormones and cytokines. Transforming growth factor beta 1 (TGFB1) is a multi-functional cytokine that we have reported to be essential for normal mammary gland development. TGFB1 is produced and secreted as part of a latent complex, and requires activation at the site of action to have biological effects. In situ hybridisation studies have shown mRNA encoding Tgfb1 is mainly expressed by mammary epithelium; however, the expression pattern of active TGFB1 in the mammary gland during different developmental stages is still unclear. Mammary gland tissue was collected from mice at puberty (5 weeks old), adult diestrus and late pregnancy (day 18 pc). Frozen sections were stained with antibody specifically reactive with active TGFB1 protein (not latent TGFB1 or other TGFB isoforms) for immunofluorescent analysis. Qualitative assessment of the staining revealed different patterns of active TGFB1 localisation depending on developmental stage. The strongest expression of active TGFB1 was observed in the mammary gland at diestrus compared to puberty and pregnancy. At diestrus, active TGFB1 was located around the surface of mammary epithelial cells. The staining was heterogeneous, with distinct zones of active TGFB1 accumulated around some but not all epithelial cells. During puberty, active TGFB1 was observed only within the lumen of the ducts. During late pregnancy, TGFB1 was homogenously distributed within the alveolar epithelium. The different patterns of active TGFB1 observed during puberty, diestrus and pregnancy suggest that TGFB1 has different roles in the mammary gland dependent on developmental stage.

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