Breast Cancer Precursors: Perturbations of Mammary Epithelial Cell Identity as a Response to Abnormal Signaling from Stromal Compartment

2014 ◽  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Stromal Compartment ◽  
Cell Identity ◽  
Cancer Precursors

scholarly journals Glucocorticoid Receptor Activation Signals through Forkhead Transcription Factor 3a in Breast Cancer Cells

2006 ◽  
Vol 20 (10) ◽  
pp. 2304-2314 ◽  
Author(s):  
Wei Wu ◽  
Min Zou ◽  
Deanna R. Brickley ◽  
Travis Pew ◽  
Suzanne D. Conzen
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Breast Cancer Cells ◽  
Receptor Activation ◽  
Mammary Epithelial ◽  
Forkhead Transcription Factor ◽  
Igfbp 3

Abstract Activation of the glucocorticoid receptor (GR) plays a critical role in the stress response of virtually all cell types. Despite recent advances in large-scale genomic and proteomic data acquisition, identification of physiologically relevant molecular events downstream of nuclear hormone receptor activation remains challenging. By analyzing gene expression changes 30 min after dexamethasone (Dex) treatment, we previously found that immediate induction of serum and glucocorticoid-regulated kinase-1 (SGK-1) expression is required for GR-mediated mammary epithelial cell survival signaling. We now report that activation of the GR mediates Forkhead transcription factor 3a (FOXO3a) phosphorylation and inactivation in mammary epithelial cells. GR-mediated induction of SGK-1 expression is required for FOXO3a inactivation; additional growth factor stimulation is not required. To further explore the gene expression changes that occur downstream of GR-mediated FOXO3a inactivation, we analyzed temporal gene expression data and selected GR-down-regulated genes containing core FOXO3a binding motifs in their proximal promoters. This approach revealed several previously unrecognized transcriptional target genes of FOXO3a, including IGF binding protein-3 (IGFBP-3). Endogenous IGFBP-3 expression was confirmed to be dependent on the GR-SGK-1-FOXO3a signaling pathway. Moreover, GR activation decreased FOXO3a-induced apoptosis in SK-BR-3 breast cancer cells. Collectively, our data suggest that GR-mediated FOXO3a inactivation is an important mechanism contributing to glucocorticoid-mediated mammary epithelial cell survival.

scholarly journals Overexpression of an N-Terminally Truncated Isoform of the Nuclear Receptor Coactivator Amplified in Breast Cancer 1 Leads to Altered Proliferation of Mammary Epithelial Cells in Transgenic Mice

2005 ◽  
Vol 19 (3) ◽  
pp. 644-656 ◽  
Author(s):  
Maddalena T. Tilli ◽  
Ronald Reiter ◽  
Annabell S. Oh ◽  
Ralf T. Henke ◽  
Kevin McDonnell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Transgenic Mice ◽  
Nuclear Receptor ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Early Gene ◽  
Nuclear Receptor Coactivator ◽  
Igf I

Abstract Amplified in breast cancer 1 (AIB1, also known as ACTR, SRC-3, RAC-3, TRAM-1, p/CIP) is a member of the p160 nuclear receptor coactivator family involved in transcriptional regulation of genes activated through steroid receptors, such as estrogen receptor α (ERα). The AIB1 gene and a more active N-terminally deleted isoform (AIB1-Δ3) are overexpressed in breast cancer. To determine the role of AIB1-Δ3 in breast cancer pathogenesis, we generated transgenic mice with human cytomegalovirus immediate early gene 1 (hCMVIE1) promoter-driven over-expression of human AIB1/ACTR-Δ3 (CMVAIB1/ACTR-Δ3 mice). AIB1/ACTR-Δ3 transgene mRNA expression was confirmed in CMV-AIB1/ACTR-Δ3 mammary glands by in situ hybridization. These mice demonstrated significantly increased mammary epithelial cell proliferation (P < 0.003), cyclin D1 expression (P = 0.002), IGF-I receptor protein expression (P = 0.026), mammary gland mass (P < 0.05), and altered expression of CCAAT/enhancer binding protein isoforms (P = 0.029). At 13 months of age, mammary ductal ectasia was found in CMV-AIB1/ACTR-Δ3 mice, but secondary and tertiary branching patterns were normal. There were no changes in the expression patterns of either ERα or Stat5a, a downstream mediator of prolactin signaling. Serum IGF-I levels were not altered in the transgenic mice. These data indicate that overexpression of the AIB1/ACTR-Δ3 isoform resulted in altered mammary epithelial cell growth. The observed changes in cell proliferation and gene expression are consistent with alterations in growth factor signaling that are thought to contribute to either initiation or progression of breast cancer. These results are consistent with the hypothesis that the N-terminally deleted isoform of AIB1 can play a role in breast cancer development and/or progression.

Fatty acid and phospholipid biosynthetic pathways are regulated throughout mammary epithelial cell differentiation and correlate to breast cancer survival

2014 ◽  
Vol 28 (10) ◽  
pp. 4247-4264 ◽  
Author(s):  
M. Luisa Dória ◽  
Ana S. Ribeiro ◽  
Jun Wang ◽  
Cândida Z. Cotrim ◽  
Pedro Domingues ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Mammary Epithelial Cell ◽  
Cancer Survival ◽  
Breast Cancer Survival ◽  
Mammary Epithelial ◽  
Biosynthetic Pathways ◽  
Epithelial Cell Differentiation

scholarly journals Integrated Single-Cell Transcriptomics and Chromatin Accessibility Analysis Reveals Regulators of Mammary Epithelial Cell Identity

Cell Reports ◽  
2020 ◽  
Vol 33 (3) ◽  
pp. 108273
Author(s):  
Nicholas Pervolarakis ◽  
Quy H. Nguyen ◽  
Justice Williams ◽  
Yanwen Gong ◽  
Guadalupe Gutierrez ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Single Cell ◽  
Mammary Epithelial Cell ◽  
Chromatin Accessibility ◽  
Mammary Epithelial ◽  
Cell Identity ◽  
Accessibility Analysis

scholarly journals Tracing anti-cancer and cancer-promoting actions of all-trans retinoic acid in breast cancer to a RARa epigenetic mechanism of mammary epithelial cell fate

Oncotarget ◽  
2016 ◽  
Vol 7 (52) ◽  
pp. 87064-87080 ◽  
Author(s):  
Stefano Rossetti ◽  
MingQiang Ren ◽  
Nicolo Visconti ◽  
Francesca Corlazzoli ◽  
Vincenzo Gagliostro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retinoic Acid ◽  
Epithelial Cell ◽  
Cell Fate ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Epigenetic Mechanism ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Anti Cancer

scholarly journals Supplementation with Fermented Barley Extract Prevents Mammary Epithelial Cell Invasion in an Early Breast Cancer Model

2021 ◽  
Vol 54 (2) ◽  
pp. 73-78
Author(s):  
Junji Itou ◽  
Akihiro Nakamura ◽  
Hideki Hokazono ◽  
Masakazu Toi
Keyword(s):  
Breast Cancer ◽  
Epithelial Cell ◽  
Early Breast Cancer ◽  
Cell Invasion ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Cancer Model ◽  
Breast Cancer Model ◽  
Epithelial Cell Invasion

The effect of calcitriol on endoplasmic reticulum stress response

2015 ◽  
Vol 93 (3) ◽  
pp. 268-271 ◽  
Author(s):  
Ela Haddur ◽  
Ali Burak Ozkaya ◽  
Handan Ak ◽  
Hikmet Hakan Aydin
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Endoplasmic Reticulum ◽  
Epithelial Cell ◽  
Er Stress ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Epithelial Cell Line ◽  
Mammary Epithelial Cell Line ◽  
Anticancer Properties

Calcitriol, the active form of vitamin D, is known for its anticancer properties including induction of apoptosis, inhibition of angiogenesis, and metastasis. Calcitriol also increases intracellular calcium triggering apoptosis in a calpain-dependent manner. Since the main storage unit for cellular calcium is endoplasmic reticulum (ER) and a decrease in ER calcium levels might induce ER stress associated cell death, we hypothesized that the cellular actions of calcitriol occur via ER stress. We have evaluated induction of ER stress by assessing BIP expression and XBP-1 splicing in breast cancer cell lines (MCF-7 and MDA-MB-231) and mammary epithelial cell line MCF10A. Our results suggest that cytotoxic concentrations of calcitriol induce an ER stress related response indicated as increased BIP levels and XBP-1 splicing not only in breast cancer cells but also in mammary epithelial cell line. However, vehicle treatment also induced a similar response de-emphasizing the importance of such effect. Calcitriol also failed to activate calpains, further weakening the idea of ER stress as the main mechanism for apoptotic effects of calcitriol. Taken together our results suggest an association between ER stress and vitamin D signaling. However present data indicates that ER stress by itself is not sufficient to explain anticancer properties of calcitriol.

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