Progesterone Receptors (PR) Mediate STAT Actions: PR and Prolactin Receptor Signaling Crosstalk in Breast Cancer Models

Publication date: Available online 23 April 2017 Source:The Journal of Steroid Biochemistry and Molecular Biology Author(s): Katherine A. Leehy, Thu H. Truong, Laura J. Mauro, Carol A. Lange Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER > PR > STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to drive malignant ...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research

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Conclusions: The observed statistically significant decrease in TDLU counts signifies increased breast epithelial involution in women with prior HDP who inherited the TT genotype of IGF1R SNP rs2016347. The increasing degree of breast involution with greater rs2016347 T allele copy number is consistent with the known progressive reduction in IGF1R expression in breast and other normal tissues. PMID: 31687025 [PubMed]
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Alveolar progenitor cells in the mammary gland are dependent on the β4 integrin. Dev Biol. 2019 Oct 03;: Authors: Walker MR, Amante JJ, Li J, Liu H, Zhu LJ, Feltri ML, Goel HL, Mercurio AM Abstract Understanding how progenitor cell function is regulated in the mammary gland is an important developmental problem that has significant implications for breast cancer. Although it had been assumed that the expression the α6β4 integrin (β4) is restricted to the basal lineage, we report that alveolar progenitor cells in the mouse mammary gland also express this integrin based on analysis ...
Source: Developmental Biology - Category: Biology Authors: Tags: Dev Biol Source Type: research
. Roose Fluidity in cell fate or heterogeneity in cell identity is an interesting cell biological phenomenon, which at the same time poses a significant obstacle for cancer therapy. The mammary gland seems a relatively straightforward organ with stromal cells and basal- and luminal- epithelial cell types. In reality, the epithelial cell fates are much more complex and heterogeneous, which is the topic of this review. Part of the complexity comes from the dynamic nature of this organ: the primitive epithelial tree undergoes extensively remodeling and expansion during puberty, pregnancy, and lactation and, unlike most ot...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Raouf The epithelial cells in an adult woman’s breast tissue are continuously replaced throughout their reproductive life during pregnancy and estrus cycles. Such extensive epithelial cell turnover is governed by the primitive mammary stem cells (MaSCs) that proliferate and differentiate into bipotential and lineage-restricted progenitors that ultimately generate the mature breast epithelial cells. These cellular processes are orchestrated by tightly-regulated paracrine signals and crosstalk between breast epithelial cells and their tissue microenvironment. However, current evidence suggests that alterations ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
ConclusionOur study provides evidence for the presence of TCs in all stages of the gland; not only in the resting stage as proved by other studies, but with immune-labeling differences suggesting different structural and physiological roles of TCs according to the stage requirements. These functions might via controlling the proliferation during pregnancy and lactation and the involution of the gland after weaning. Thus, more future functional studies of TCs will be important to help understanding the mechanism by which TCs contribute to tissue homeostasis concerning the role of the stromal/epithelial interactions in mamma...
Source: Life Sciences - Category: Biology Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Li Liu, Jiajing Lin and Hongying He* Department of Obstetrics and Gynecology, Liuzhou Worker’s Hospital, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, China Background and Objective: Endometrial cancer (EC) is a common gynecological malignancy worldwide. Despite advances in the development of strategies for treating EC, prognosis of the disease remains unsatisfactory, especially for advanced EC. The aim of this study was to identify novel genes that can be used as potential biomarkers for identifying the prognosis of EC and to construct a novel risk stratification using these genes. Me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Tereza DÄ›dová1,2, Elena Iona Braicu3, Jalid Sehouli3 and Véronique Blanchard1* 1Institute of Laboratory Medicine, Clinical Chemistry and Pathobiochemistry, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany 2Department of Biology, Chemistry and Pharmacy, Freie Universität Berlin, Berlin, Germany 3Department of Gynecology, European Competence Center for Ovarian Cancer, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Be...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 5 April 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Faegheh Ghanbari, Andrea Hebert-Losier, Janelle Barry, Donald Poirier, Vincent Giguere, Sylvie Mader, Anie PhilipAbstractEstrogen-receptor related receptors (ERRs) which consists of ERRα, ERRβ and ERRγ belong to the orphan nuclear receptor subfamily 3, group B (NR3B) subfamily, and are constitutively active. ERRs have been shown to actively modulate estrogenic responses, and to play an essential role in pregnancy, and are implicated in breast cancer progression. Despite intensive effor...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research
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