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 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.

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.

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.

Stem Cells in Normal Mammary Gland and Breast Cancer

2010 ◽  
Vol 339 (4) ◽  
pp. 366-370 ◽  
Author(s):  
Jie Luo ◽  
Tao Ma ◽  
Jun Lu ◽  
Xin Yin
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mammary Gland ◽  
Normal Mammary Gland

scholarly journals Early Steps of Mammary Stem Cell Transformation by Exogenous Signals; Effects of Bisphenol Endocrine Disrupting Chemicals and Bone Morphogenetic Proteins

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1351 ◽  
Author(s):  
Nora Jung ◽  
Veronique Maguer-Satta ◽  
Boris Guyot
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Mammary Gland ◽  
Bone Morphogenetic Proteins ◽  
Mammary Gland Development ◽  
Cell Transformation ◽  
Current Knowledge ◽  
Endocrine Disrupting Chemicals ◽  
Normal Mammary Gland ◽  
Gland Development

Estrogens are major regulators of the mammary gland development, notably during puberty, via estrogen receptor (ER) activation, leading to the proliferation and differentiation of mammary cells. In addition to estrogens, the bone morphogenetic proteins (BMPs) family is involved in breast stem cell/progenitor commitment. However, these two pathways that synergistically contribute to the biology of the normal mammary gland have also been described to initiate and/or promote breast cancer development. In addition to intrinsic events, lifestyle habits and exposure to environmental cues are key risk factors for cancer in general, and especially for breast cancer. In the latter case, bisphenol A (BPA), an estrogen-mimetic compound, is a critical pollutant both in terms of the quantities released in our environment and of its known and speculated effects on mammary gland biology. In this review, we summarize the current knowledge on the actions of BMPs and estrogens in both normal mammary gland development and breast cancer initiation, dissemination, and resistance to treatment, focusing on the dysregulations of these processes by BPA but also by other bisphenols, including BPS and BPF, initially considered as safer alternatives to BPA.

scholarly journals Tissue architecture and breast cancer: the role of extracellular matrix and steroid hormones.

2000 ◽  
pp. 95-113 ◽  
Author(s):  
R K Hansen ◽  
M J Bissell
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Mammary Gland ◽  
Signaling Pathways ◽  
Steroid Hormones ◽  
Cancer Therapeutics ◽  
Normal Mammary Gland ◽  
Tissue Architecture ◽  
Steroid Hormone Signaling ◽  
And Function

The changes in tissue architecture that accompany the development of breast cancer have been the focus of investigations aimed at developing new cancer therapeutics. As we learn more about the normal mammary gland, we have begun to understand the complex signaling pathways underlying the dramatic shifts in the structure and function of breast tissue. Integrin-, growth factor-, and steroid hormone-signaling pathways all play an important part in maintaining tissue architecture; disruption of the delicate balance of signaling results in dramatic changes in the way cells interact with each other and with the extracellular matrix, leading to breast cancer. The extracellular matrix itself plays a central role in coordinating these signaling processes. In this review, we consider the interrelationships between the extracellular matrix, integrins, growth factors, and steroid hormones in mammary gland development and function.

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