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Article ; Online: High FOXA1 levels induce ER transcriptional reprogramming, a pro-metastatic secretome, and metastasis in endocrine-resistant breast cancer.

2023 Volume 42, Issue 8, Page(s) 112821

Abstract: Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor- ... ...

Abstract	Aberrant activation of the forkhead protein FOXA1 is observed in advanced hormone-related cancers. However, the key mediators of high FOXA1 signaling remain elusive. We demonstrate that ectopic high FOXA1 (H-FOXA1) expression promotes estrogen receptor-positive (ER+) breast cancer (BC) metastasis in a xenograft mouse model. Mechanistically, H-FOXA1 reprograms ER-chromatin binding to elicit a core gene signature (CGS) enriched in ER+ endocrine-resistant (EndoR) cells. We identify Secretome14, a CGS subset encoding ER-dependent cancer secretory proteins, as a strong predictor for poor outcomes of ER+ BC. It is elevated in ER+ metastases vs. primary tumors, irrespective of ESR1 mutations. Genomic ER binding near Secretome14 genes is also increased in mutant ER-expressing or mitogen-treated ER+ BC cells and in ER+ metastatic vs. primary tumors, suggesting a convergent pathway including high growth factor receptor signaling in activating pro-metastatic secretome genes. Our findings uncover H-FOXA1-induced ER reprogramming that drives EndoR and metastasis partly via an H-FOXA1/ER-dependent secretome.
Language	English
Publishing date	2023-07-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112821
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Article ; Online: A novel role of ADGRF1 (GPR110) in promoting cellular quiescence and chemoresistance in human epidermal growth factor receptor 2-positive breast cancer.

Abdulkareem, Noor Mazin / Bhat, Raksha / Qin, Lanfang / Vasaikar, Suhas / Gopinathan, Ambily / Mitchell, Tamika / Shea, Martin J / Nanda, Sarmistha / Thangavel, Hariprasad / Zhang, Bing / De Angelis, Carmine / Schiff, Rachel / Trivedi, Meghana V

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2021 Volume 35, Issue 7, Page(s) e21719

Abstract: While G protein-coupled receptors (GPCRs) are known to be excellent drug targets, the second largest family of adhesion-GPCRs is less explored for their role in health and disease. ADGRF1 (GPR110) is an adhesion-GPCR and has an important function in ... ...

Abstract	While G protein-coupled receptors (GPCRs) are known to be excellent drug targets, the second largest family of adhesion-GPCRs is less explored for their role in health and disease. ADGRF1 (GPR110) is an adhesion-GPCR and has an important function in neurodevelopment and cancer. Despite serving as a poor predictor of survival, ADGRF1's coupling to G proteins and downstream pathways remain unknown in cancer. We evaluated the effects of ADGRF1 overexpression on tumorigenesis and signaling pathways using two human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC) cell-line models. We also interrogated publicly available clinical datasets to determine the expression of ADGRF1 in various BC subtypes and its impact on BC-specific survival (BCSS) and overall survival (OS) in patients. ADGRF1 overexpression in HER2+ BC cells increased secondary mammosphere formation, soft agar colony formation, and % of Aldefluor-positive tumorigenic population in vitro and promoted tumor growth in vivo. ADGRF1 co-immunoprecipitated with both Gαs and Gαq proteins and increased cAMP and IP1 when overexpressed. However, inhibition of only the Gαs pathway by SQ22536 reversed the pro-tumorigenic effects of ADGRF1 overexpression. RNA-sequencing and RPPA analysis revealed inhibition of cell cycle pathways with ADGRF1 overexpression, suggesting cellular quiescence, as also evidenced by cell cycle arrest at the G0/1 phase and resistance to chemotherapy in HER2+ BC. ADGRF1 was significantly overexpressed in the HER2-enriched BC compared to luminal A and B subtypes and predicted worse BCSS and OS in these patients. Therefore, ADGRF1 represents a novel drug target in HER2+ BC, warranting discovery of novel ADGRF1 antagonists.
MeSH term(s)	Animals ; Breast Neoplasms/genetics ; Carcinogenesis/genetics ; Cell Cycle Checkpoints/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Drug Resistance, Neoplasm/genetics ; Female ; G1 Phase/genetics ; Humans ; Mice ; Mice, Nude ; Oncogene Proteins/genetics ; Receptor, ErbB-2/genetics ; Receptors, G-Protein-Coupled/genetics ; Resting Phase, Cell Cycle/genetics ; Signal Transduction/genetics
Chemical Substances	ADGRF1 protein, human ; Oncogene Proteins ; Receptors, G-Protein-Coupled ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2021-06-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202100070R
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Zs.A 2266: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: In vivo longitudinal imaging of RNA interference-induced endocrine therapy resistance in breast cancer.

Biswal, Nrusingh C / Fu, Xiaoyong / Jagtap, Jaidip M / Shea, Martin J / Kumar, Vijetha / Lords, Tamika / Roy, Ronita / Schiff, Rachel / Joshi, Amit

Journal of biophotonics

2019 Volume 13, Issue 1, Page(s) e201900180

Abstract: Endocrine therapy resistance in breast cancer is a major obstacle in the treatment of patients with estrogen receptor-positive (ER+) tumors. Herein, we demonstrate the feasibility of longitudinal, noninvasive and semiquantitative in vivo molecular ... ...

Abstract	Endocrine therapy resistance in breast cancer is a major obstacle in the treatment of patients with estrogen receptor-positive (ER+) tumors. Herein, we demonstrate the feasibility of longitudinal, noninvasive and semiquantitative in vivo molecular imaging of resistance to three endocrine therapies by using an inducible fluorescence-labeled short hairpin RNA (shRNA) system in orthotopic mice xenograft tumors. We employed a dual fluorescent doxycycline (Dox)-regulated lentiviral inducer system to transfect ER+ MCF7L breast cancer cells, with green fluorescent protein (GFP) expression as a marker of transfection and red fluorescent protein (RFP) expression as a surrogate marker of Dox-induced tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) knockdown. Xenografted MCF7L tumor-bearing nude mice were randomized to therapies comprising estrogen deprivation, tamoxifen or an ER degrader (fulvestrant) and an estrogen-treated control group. Longitudinal imaging was performed by a home-built multispectral imaging system based on a cooled image intensified charge coupled device camera. The GFP signal, which corresponds to number of viable tumor cells, exhibited excellent correlation to caliper-measured tumor size (P << .05). RFP expression was substantially higher in mice exhibiting therapy resistance and strongly and significantly (P < 1e-7) correlated with the tumor size progression for the mice with shRNA-induced PTEN knockdown. PTEN loss was strongly correlated with resistance to estrogen deprivation, tamoxifen and fulvestrant therapies.
MeSH term(s)	Animals ; Antineoplastic Agents, Hormonal/pharmacology ; Antineoplastic Agents, Hormonal/therapeutic use ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Female ; Humans ; Mice ; Mice, Nude ; RNA Interference
Chemical Substances	Antineoplastic Agents, Hormonal
Language	English
Publishing date	2019-10-09
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2390063-5
ISSN	1864-0648 ; 1864-063X
ISSN (online)	1864-0648
ISSN	1864-063X
DOI	10.1002/jbio.201900180
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Zs.A 6723: Show issues

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Article ; Online: Therapeutic Targeting of Nemo-like Kinase in Primary and Acquired Endocrine-resistant Breast Cancer.

Wang, Xian / Veeraraghavan, Jamunarani / Liu, Chia-Chia / Cao, Xixi / Qin, Lanfang / Kim, Jin-Ah / Tan, Ying / Loo, Suet Kee / Hu, Yiheng / Lin, Ling / Lee, Sanghoon / Shea, Martin J / Mitchell, Tamika / Li, Shunqiang / Ellis, Matthew J / Hilsenbeck, Susan G / Schiff, Rachel / Wang, Xiao-Song

Clinical cancer research : an official journal of the American Association for Cancer Research

2021 Volume 27, Issue 9, Page(s) 2648–2662

Abstract: Purpose: Endocrine resistance remains a major clinical challenge in estrogen receptor (ER)-positive breast cancer. Despite the encouraging results from clinical trials for the drugs targeting known survival signaling, relapse is still inevitable. There ... ...

Abstract	Purpose: Endocrine resistance remains a major clinical challenge in estrogen receptor (ER)-positive breast cancer. Despite the encouraging results from clinical trials for the drugs targeting known survival signaling, relapse is still inevitable. There is an unmet need to discover new drug targets in the unknown escape pathways. Here, we report Nemo-like kinase (NLK) as a new actionable kinase target that endows previously uncharacterized survival signaling in endocrine-resistant breast cancer. Experimental design: The effects of NLK inhibition on the viability of endocrine-resistant breast cancer cell lines were examined by MTS assay. The effect of VX-702 on NLK activity was verified by kinase assay. The modulation of ER and its coactivator, SRC-3, by NLK was examined by immunoprecipitation, kinase assay, luciferase assay, and RNA sequencing. The therapeutic effects of VX-702 and everolimus were tested on cell line- and patient-derived xenograft (PDX) tumor models. Results: NLK overexpression endows reduced endocrine responsiveness and is associated with worse outcome of patients treated with tamoxifen. Mechanistically, NLK may function, at least in part, via enhancing the phosphorylation of ERα and its key coactivator, SRC-3, to modulate ERα transcriptional activity. Through interrogation of a kinase profiling database, we uncovered and verified a highly selective dual p38/NLK inhibitor, VX-702. Coadministration of VX-702 with the mTOR inhibitor, everolimus, demonstrated a significant therapeutic effect in cell line-derived xenograft and PDX tumor models of acquired or Conclusions: Together, this study reveals the potential of therapeutic modulation of NLK for the management of the endocrine-resistant breast cancers with active NLK signaling.
MeSH term(s)	Animals ; Antineoplastic Agents, Hormonal/pharmacology ; Antineoplastic Agents, Hormonal/therapeutic use ; Biomarkers, Tumor ; Breast Neoplasms/diagnosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/etiology ; Breast Neoplasms/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm/drug effects ; Estrogen Receptor alpha/metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Phosphorylation ; Prognosis ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction/drug effects ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents, Hormonal ; Biomarkers, Tumor ; Estrogen Receptor alpha ; Protein Kinase Inhibitors ; NLK protein, human (EC 2.7.1.-) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-20-2961
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Zs.A 4223: Show issues

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Article: Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models.

NPJ breast cancer

2021 Volume 7, Issue 1, Page(s) 63

Abstract: Lapatinib (L) plus trastuzumab (T), with endocrine therapy for estrogen receptor (ER)+ tumors, but without chemotherapy, yielded meaningful response in HER2+ breast cancer (BC) neoadjuvant trials. The irreversible/pan-HER inhibitor neratinib (N) has ... ...

Abstract	Lapatinib (L) plus trastuzumab (T), with endocrine therapy for estrogen receptor (ER)+ tumors, but without chemotherapy, yielded meaningful response in HER2+ breast cancer (BC) neoadjuvant trials. The irreversible/pan-HER inhibitor neratinib (N) has proven more potent than L. However, the efficacy of N+T in comparison to pertuzumab (P) + T or L + T (without chemotherapy) remains less studied. To address this, mice bearing HER2+ BT474-AZ (ER+) cell and BCM-3963 patient-derived BC xenografts were randomized to vehicle, N, T, P, N+T, or P+T, with simultaneous estrogen deprivation for BT474-AZ. Time to tumor regression/progression and incidence/time to complete response (CR) were determined. Changes in key HER pathway and proliferative markers were assessed by immunohistochemistry and western blot of short-term-treated tumors. In the BT474-AZ model, while all N, P, T, N + T, and P + T treated tumors regressed, N + T-treated tumors regressed faster than P, T, and P + T. Further, N + T was superior to N and T alone in accelerating CR. In the BCM-3963 model, which was refractory to T, P, and P + T, while N and N + T yielded 100% CR, N + T accelerated the CR compared to N. Ki67, phosphorylated (p) AKT, pS6, and pERK levels were largely inhibited by N and N + T, but not by T, P, or P + T. Phosphorylated HER receptor levels were also markedly inhibited by N and N + T, but not by P + T or L + T. Our findings establish the efficacy of combining N with T and support clinical testing to investigate the efficacy of N + T with or without chemotherapy in the neoadjuvant setting for HER2+ BC.
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Journal Article
ISSN	2374-4677
ISSN	2374-4677
DOI	10.1038/s41523-021-00274-0
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Article ; Online: The oral selective oestrogen receptor degrader (SERD) AZD9496 is comparable to fulvestrant in antagonising ER and circumventing endocrine resistance.

Nardone, Agostina / Weir, Hazel / Delpuech, Oona / Brown, Henry / De Angelis, Carmine / Cataldo, Maria Letizia / Fu, Xiaoyong / Shea, Martin J / Mitchell, Tamika / Veeraraghavan, Jamunarani / Nagi, Chandandeep / Pilling, Mark / Rimawi, Mothaffar F / Trivedi, Meghana / Hilsenbeck, Susan G / Chamness, Gary C / Jeselsohn, Rinath / Osborne, C Kent / Schiff, Rachel

British journal of cancer

2018 Volume 120, Issue 3, Page(s) 331–339

Abstract: Background: The oestrogen receptor (ER) is an important therapeutic target in ER-positive (ER+) breast cancer. The selective ER degrader (SERD), fulvestrant, is effective in patients with metastatic breast cancer, but its intramuscular route of ... ...

Abstract	Background: The oestrogen receptor (ER) is an important therapeutic target in ER-positive (ER+) breast cancer. The selective ER degrader (SERD), fulvestrant, is effective in patients with metastatic breast cancer, but its intramuscular route of administration and low bioavailability are major clinical limitations. Methods: Here, we studied the pharmacology of a new oral SERD, AZD9496, in a panel of in vitro and in vivo endocrine-sensitive and -resistant breast cancer models. Results: In endocrine-sensitive models, AZD9496 inhibited cell growth and blocked ER activity in the presence or absence of oestrogen. In vivo, in the presence of oestrogen, short-term AZD9496 treatment, like fulvestrant, resulted in tumour growth inhibition and reduced expression of ER-dependent genes. AZD9496 inhibited cell growth in oestrogen deprivation-resistant and tamoxifen-resistant cell lines and xenograft models that retain ER expression. AZD9496 effectively reduced ER levels and ER-induced transcription. Expression analysis of short-term treated tumours showed that AZD9496 potently inhibited classic oestrogen-induced gene transcription, while simultaneously increasing expression of genes negatively regulated by ER, including genes potentially involved in escape pathways of endocrine resistance. Conclusions: These data suggest that AZD9496 is a potent anti-oestrogen that antagonises and degrades ER with anti-tumour activity in both endocrine-sensitive and endocrine-resistant models.
MeSH term(s)	Animals ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Proliferation/drug effects ; Cinnamates/administration & dosage ; Drug Resistance, Neoplasm/drug effects ; Estradiol/genetics ; Estradiol/metabolism ; Estrogens/genetics ; Estrogens/metabolism ; Female ; Fulvestrant/administration & dosage ; Heterografts ; Humans ; Indoles/administration & dosage ; MCF-7 Cells ; Mice ; Neoplasms, Hormone-Dependent/drug therapy ; Neoplasms, Hormone-Dependent/genetics ; Receptors, Estrogen/antagonists & inhibitors ; Receptors, Estrogen/genetics ; Tamoxifen/administration & dosage
Chemical Substances	AZD9496 ; Cinnamates ; Estrogens ; Indoles ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45) ; Fulvestrant (22X328QOC4) ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2018-12-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-018-0354-9
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Article ; Online: An epigenomic approach to therapy for tamoxifen-resistant breast cancer.

Feng, Qin / Zhang, Zheng / Shea, Martin J / Creighton, Chad J / Coarfa, Cristian / Hilsenbeck, Susan G / Lanz, Rainer / He, Bin / Wang, Lei / Fu, Xiaoyong / Nardone, Agostina / Song, Yongcheng / Bradner, James / Mitsiades, Nicholas / Mitsiades, Constantine S / Osborne, C Kent / Schiff, Rachel / O'Malley, Bert W

Cell research

2014 Volume 24, Issue 7, Page(s) 809–819

Abstract: Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the growth of breast cancer cells with ... ...

Abstract	Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance, suggesting that ERα remains a valid target for treatment of tamoxifen-resistant (Tam-R) breast cancer. In an effort to identify novel regulators of ERα signaling, through a small-scale siRNA screen against histone methyl modifiers, we found WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling in breast cancer cells. We demonstrated that WHSC1 is recruited to the ERα gene by the BET protein BRD3/4, and facilitates ERα gene expression. The small-molecule BET protein inhibitor JQ1 potently suppressed the classic ERα signaling pathway and the growth of Tam-R breast cancer cells in culture. Using a Tam-R breast cancer xenograft mouse model, we demonstrated in vivo anti-breast cancer activity by JQ1 and a strong long-lasting effect of combination therapy with JQ1 and the ER degrader fulvestrant. Taken together, we provide evidence that the epigenomic proteins BRD3/4 and WHSC1 are essential regulators of estrogen receptor signaling and are novel therapeutic targets for treatment of Tam-R breast cancer.
MeSH term(s)	Animals ; Azepines/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Cell Cycle Proteins ; Cell Line, Tumor ; Drug Resistance, Neoplasm/drug effects ; Epigenomics ; Estradiol/analogs & derivatives ; Estradiol/therapeutic use ; Estrogen Receptor alpha/biosynthesis ; Estrogen Receptor alpha/physiology ; Female ; Fulvestrant ; Histone-Lysine N-Methyltransferase/metabolism ; Humans ; Mice ; Nuclear Proteins/physiology ; RNA-Binding Proteins/physiology ; Repressor Proteins/metabolism ; Signal Transduction/drug effects ; Tamoxifen/pharmacology ; Tamoxifen/therapeutic use ; Transcription Factors/physiology ; Triazoles/therapeutic use
Chemical Substances	(+)-JQ1 compound ; Azepines ; BRD3 protein, human ; BRD4 protein, human ; Cell Cycle Proteins ; ESR1 protein, human ; Estrogen Receptor alpha ; Nuclear Proteins ; RNA-Binding Proteins ; Repressor Proteins ; Transcription Factors ; Triazoles ; Tamoxifen (094ZI81Y45) ; Fulvestrant (22X328QOC4) ; Estradiol (4TI98Z838E) ; Histone-Lysine N-Methyltransferase (EC 2.1.1.43) ; NSD2 protein, human (EC 2.1.1.43)
Language	English
Publishing date	2014-05-30
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/cr.2014.71
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Zs.A 5283: Show issues

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Article ; Online: Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer.

Science translational medicine

2014 Volume 6, Issue 229, Page(s) 229ra41

Abstract: Resistance to aromatase inhibitors (AIs) is a major clinical problem in the treatment of estrogen receptor (ER)-positive breast cancer. In two breast cancer cell line models of AI resistance, we identified widespread DNA hyper- and hypomethylation, with ... ...

Abstract	Resistance to aromatase inhibitors (AIs) is a major clinical problem in the treatment of estrogen receptor (ER)-positive breast cancer. In two breast cancer cell line models of AI resistance, we identified widespread DNA hyper- and hypomethylation, with enrichment for promoter hypermethylation of developmental genes. For the homeobox gene HOXC10, methylation occurred in a CpG shore, which overlapped with a functional ER binding site, causing repression of HOXC10 expression. Although short-term blockade of ER signaling caused relief of HOXC10 repression in both cell lines and breast tumors, it also resulted in concurrent recruitment of EZH2 and increased H3K27me3, ultimately transitioning to increased DNA methylation and silencing of HOXC10. Reduced HOXC10 in vitro and in xenografts resulted in decreased apoptosis and caused antiestrogen resistance. Supporting this, we used paired primary and metastatic breast cancer specimens to show that HOXC10 was reduced in tumors that recurred during AI treatment. We propose a model in which estrogen represses apoptotic and growth-inhibitory genes such as HOXC10, contributing to tumor survival, whereas AIs induce these genes to cause apoptosis and therapeutic benefit, but long-term AI treatment results in permanent repression of these genes via methylation and confers resistance. Therapies aimed at inhibiting AI-induced histone and DNA methylation may be beneficial in blocking or delaying AI resistance.
MeSH term(s)	Animals ; Apoptosis/drug effects ; Apoptosis/genetics ; Aromatase Inhibitors/pharmacology ; Aromatase Inhibitors/therapeutic use ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Movement/drug effects ; Cell Movement/genetics ; Cell Proliferation/drug effects ; Cellular Reprogramming/drug effects ; Cellular Reprogramming/genetics ; DNA Methylation/drug effects ; DNA Methylation/genetics ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Epigenesis, Genetic/drug effects ; Epigenesis, Genetic/genetics ; Estrogens/pharmacology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Silencing/drug effects ; Histones/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; MCF-7 Cells ; Mice ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/genetics ; Neoplasm Recurrence, Local/pathology ; Promoter Regions, Genetic ; Xenograft Model Antitumor Assays
Chemical Substances	Aromatase Inhibitors ; Estrogens ; HOXC10 protein, human ; Histones ; Homeodomain Proteins
Language	English
Publishing date	2014-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.3008326
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