scholarly journals Early exposure of the rat mammary gland to estrogen and progesterone blocks co-localization of estrogen receptor expression and proliferation

2001 ◽  
Vol 171 (1) ◽  
pp. 75-83 ◽  
Author(s):  
L Sivaraman ◽  
SG Hilsenbeck ◽  
L Zhong ◽  
J Gay ◽  
OM Conneely ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Mammary Gland ◽  
Protective Effect ◽  
Tumor Development ◽  
Positive Association ◽  
Receptor Expression ◽  
Target Cells ◽  
Proliferating Cells ◽  
Estrogen Receptor Positive ◽  
Er Positive

An early single full-term pregnancy induces a long-lasting protective effect against mammary tumor development in humans and rodents. This protective effect can be mimicked in rats by short-term administration of estrogen and progesterone hormones prior to carcinogen administration. The hormones of pregnancy are able to induce a proliferative block upon carcinogen challenge that is not observed in the age-matched virgin. We wished to determine whether carcinogen is needed to induce a paracrine-to-autocrine shift of proliferation in steroid receptor positive cells or if such a cell population already exists in the age-matched virgin mammary gland. Here we show that estrogen receptor positive (ER+) proliferating cells are rare in the developing mammary gland of the virgin rat but represent the majority of the proliferating cells in the mature (96-day-old) mammary gland of the virgin rat. As the majority of the proliferating cells before carcinogen challenge were ER positive, the ER+ proliferating cells in the mature mammary gland may represent the target cells for carcinogen-induced transformation. Importantly, prior exposure of the mammary gland to pregnancy levels of estrogen/progesterone blocked this positive association. This ability to block the proliferation of the ER+ cells may be one factor by which pregnancy induces protection against breast cancer.

scholarly journals Targeting Palbociclib-Resistant Estrogen Receptor-Positive Breast Cancer Cells via Oncolytic Virotherapy

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 684 ◽  
Author(s):  
Nadiia Lypova ◽  
Lilibeth Lanceta ◽  
Alana Gipson ◽  
Stephanie Vega ◽  
Rodolfo Garza-Morales ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Viral Entry ◽  
Metastatic Breast ◽  
Receptor Expression ◽  
Type I ◽  
Development Of Resistance ◽  
Estrogen Receptor Positive ◽  
Entry Receptor ◽  
Resistant Cells

While clinical responses to palbociclib have been promising, metastatic breast cancer remains incurable due to the development of resistance. We generated estrogen receptor-positive (ER+) and ER-negative (ER−) cell line models and determined their permissiveness and cellular responses to an oncolytic adenovirus (OAd) known as Ad5/3-delta24. Analysis of ER+ and ER− palbociclib-resistant cells revealed two clearly distinguishable responses to the OAd. While ER+ palbociclib-resistant cells displayed a hypersensitive phenotype to the effects of the OAd, ER− palbociclib-resistant cells showed a resistant phenotype to the OAd. Hypersensitivity to the OAd in ER+ palbociclib-resistant cells correlated with a decrease in type I interferon (IFN) signaling, an increase in viral entry receptor expression, and an increase in cyclin E expression. OAd resistance in ER− palbociclib-resistant cells correlated with an increase in type I IFN signaling and a marked decrease in viral entry receptor. Using the OAd as monotherapy caused significant cytotoxicity to both ER+ and ER− palbociclib-sensitive cell lines. However, the addition of palbociclib increased the oncolytic activity of the OAd only in ER+ palbociclib-sensitive cells. Our studies provide a mechanistic base for a novel anti-cancer regimen composed of an OAd in combination with palbociclib for the treatment of ER+ breast cancer.

scholarly journals Immunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers

2020 ◽  
pp. 767-779
Author(s):  
Tess O’Meara ◽  
Michal Marczyk ◽  
Tao Qing ◽  
Vesal Yaghoobi ◽  
Kim Blenman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Molecular Taxonomy ◽  
Validation Data ◽  
Activation Markers ◽  
Estrogen Receptor Positive ◽  
Er Positive ◽  
Immune Related Genes

PURPOSE A subset of estrogen receptor–positive (ER-positive) breast cancer (BC) contains high levels of tumor-infiltrating lymphocytes (TILs), similar to triple-negative BC (TNBC). The majority of immuno-oncology trials target TNBCs because of the greater proportion of TIL-rich TNBCs. The extent to which the immune microenvironments of immune-rich ER-positive BC and TNBC differ is unknown. PATIENTS AND METHODS RNA sequencing data from The Cancer Genome Atlas (TCGA; n = 697 ER-positive BCs; n = 191 TNBCs) were used for discovery; microarray expression data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1,186 ER-positive BCs; n = 297 TNBCs) was used for validation. Patients in the top 25th percentile of a previously published total TIL metagene score distribution were considered immune rich. We compared expression of immune cell markers, immune function metagenes, and immuno-oncology therapeutic targets among immune-rich subtypes. RESULTS Relative fractions of resting mast cells (TCGA Padj = .009; METABRIC Padj = 4.09E-15), CD8+ T cells (TCGA Padj = .015; METABRIC Padj = 0.390), and M2-like macrophages (TCGA Padj= 4.68E-05; METABRIC Padj = .435) were higher in immune-rich ER-positive BCs, but M0-like macrophages (TCGA Padj = 0.015; METABRIC Padj = .004) and M1-like macrophages (TCGA Padj = 9.39E-08; METABRIC Padj = 6.24E-11) were higher in immune-rich TNBCs. Ninety-one immune-related genes (eg, CXCL14, CSF3R, TGF-B3, LRRC32/GARP, TGFB-R2) and a transforming growth factor β (TGF-β) response metagene were significantly overexpressed in immune-rich ER-positive BCs, whereas 41 immune-related genes (eg, IFNG, PD-L1, CTLA4, MAGEA4) were overexpressed in immune-rich TNBCs in both discovery and validation data sets. TGF-β pathway member genes correlated negatively with expression of immune activation markers ( IFNG, granzyme-B, perforin) and positively with M2-like macrophages ( IL4, IL10, and MMP9) and regulatory T-cell ( FOXP3) markers in both subtypes. CONCLUSION Different immunotherapy strategies may be optimal in immune-rich ER-positive BC and TNBC. Drugs targeting the TGF-β pathway and M2-like macrophages are promising strategies in immune-rich ER-positive BCs to augment antitumor immunity.

scholarly journals Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers

2010 ◽  
Vol 124 (3) ◽  
pp. 607-617 ◽  
Author(s):  
Isabella Castellano ◽  
Elena Allia ◽  
Valeria Accortanzo ◽  
Anna Maria Vandone ◽  
Luigi Chiusa ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Prognostic Factor ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Significant Prognostic Factor ◽  
Breast Cancers ◽  
Estrogen Receptor Positive
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