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Abstract 2435: FGFR1 is associated with resistance to interaction with estrogen receptor (ER) {alpha} endocrine therapy in ER+/FGFR1-amplified breast cancer
Conclusions: These data suggest FGFR1 binds ER and regulates ligand-independent ER transcriptional activity. This role depends on the FGFR1 kinase activity and may involve its association with cyclin D1. These interactions may explain the endocrine resistance reported in ER+/FGFR1 amplified breast cancers and suggest these tumors should be treated with a combination of antiestrogen and FGFR inhibitors.Citation Format: Luigi Formisano, Christian D. Young, Neil Bhola, Jennifer M. Giltnane, Monica V. Estrada, Carlos L. Arteaga. FGFR1 is associated with resistance to interaction with estrogen receptor (ER) α endocrine therapy...
Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Formisano, L., Young, C. D., Bhola, N., Giltnane, J. M., Estrada, M. V., Arteaga, C. L. Tags: Clinical Research (Excluding Clinical Trials) Source Type: research

Abstract S3-03: Nuclear FGFR1 interaction with estrogen receptor (ER) {alpha} is associated with resistance to endocrine therapy in ER+/FGFR1-amplified breast cancer
Conclusions: These data support a critical role of ER and FGFR1 interaction in endocrine resistance in ER+/FGFR1-amplified breast cancer. Targeting of FGFR1 in combination with antiestrogens may abrogate resistance to endocrine therapy in these tumors and is worthy of clinical investigation.Citation Format: Formisano L, Young CD, Bhola NE, Bulen B, Estrada VM, Wagle N, Van Allen E, Red Brewer ML, Jansen VM, Guerrero AL, Giltnane JM, Strcker T, Arteaga CL. Nuclear FGFR1 interaction with estrogen receptor (ER) α is associated with resistance to endocrine therapy in ER+/FGFR1-amplified breast cancer. [abstract]. In: Proceedi...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Formisano, L., Young, C., Bhola, N., Bulen, B., Estrada, V., Wagle, N., Van Allen, E., Red Brewer, M., Jansen, V., Guerrero, A., Giltnane, J., Strcker, T., Arteaga, C. Tags: General Session Abstracts Source Type: research

Abstract P1-08-03: Identification and characterization of a novel endoxifen substrate, PKC{beta}1, and its interaction with the estrogen receptor
Conclusions: Our findings demonstrated that endoxifen binds and inhibits PKCβ1 at relevant concentrations achieved in the endoxifen clinical trial studies. PKCβ1 interacts with cytoplasmic ERα and PKCβ1 knockdown inhibits cell proliferation and enhances ERα turnover. However, in PKCβ1 overexpressing cells, PKCβ1 may exhibit tumor suppressive effects. These data suggest a complex interaction between PKCβ1 and ERα and that endoxifen's effects on PKCβ1 may alter drug response of endocrine therapy. Further studies are ongoing to characterize the role of PKCβ1 and its role in ER biology and response to endoxifen.Cita...
Source: Cancer Research - February 13, 2017 Category: Cancer & Oncology Authors: C Guo, MJ Kuffel, RA Kudgus, Z Huang, AM Bode, J Cheng, VJ Suman, JM Reid, ES Bruinsma, M Subramaniam, MM Ames, JR Hawse, MP Goetz Tags: Poster Session Abstracts Source Type: research

Abstract P4-10-02: Transmembrane protein 33 (TMEM33) induces apoptosis via UPR signaling and autophagy in breast cancer cells
Conclusions: Our findings demonstrated that endoxifen binds and inhibits PKCβ1 at relevant concentrations achieved in the endoxifen clinical trial studies. PKCβ1 interacts with cytoplasmic ERα and PKCβ1 knockdown inhibits cell proliferation and enhances ERα turnover. However, in PKCβ1 overexpressing cells, PKCβ1 may exhibit tumor suppressive effects. These data suggest a complex interaction between PKCβ1 and ERα and that endoxifen's effects on PKCβ1 may alter drug response of endocrine therapy. Further studies are ongoing to characterize the role of PKCβ1 and its role in ER biology and response to endoxifen.Cita...
Source: Cancer Research - February 13, 2017 Category: Cancer & Oncology Authors: R Clarke, R Hu, X Zhang, L Hilakivi-Clarke, U Kasid Tags: Poster Session Abstracts Source Type: research

Abstract 2739: Specific interaction of human MGMT with ER-{alpha} in breast cancer cells: Co-degradation of MGMT and ER- {alpha} proteins by either fulvestrant or O6-benzylguanine and its therapeutic significance
This study investigated whether i) MGMT is modulated by endocrine therapies, ii) MGMT interacts with ER-signaling components and iii) if such findings are exploitable for improved breast cancer treatment. The ER-α positive cell lines MCF-7, T47D and ER- α negative MDAMB 468 cells, all MGMT-proficient, were treated with Fulvestrant (Faslodex, ICI 182, 780) or O6-benzylguanine (BG) in various experiments. Fulvestrant is a pure antiestrogen that binds to ER without eliciting any transcriptional effects, but leads to the receptor degradation through the ubiquitin-proteasome (ub-P) pathway. BG is a specific pseudosubstrate fo...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Srivenugopal, K. S., Paranjpe, A. Tags: Experimental and Molecular Therapeutics Source Type: research

Abstract 4227: The ribonucleotide reductase inhibitor Didox reverses tamoxifen resistance in breast cancer cells
In this study, we report that the inhibition of RRM2 by the small molecule inhibitor of ribonucleotide reductase activity Didox (3, 4-dihydroxybenzohydroxamic acid), significantly reduced tamoxifen induced cell proliferation in AKT overexpressing cells and tamoxifen resistant tumors generated by these cells. As well, Didox in combination with tamoxifen also inhibited cell proliferation in acquired tamoxifen resistant breast cancer cell lines. Employing comprehensive cell culture and in vivo models, we demonstrate that combining tamoxifen with Didox may reverse tamoxifen resistance in AKT expressing breast cancer cells. Cit...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Shah, K. N., Elford, H. L., Faridi, J. S. Tags: Molecular and Cellular Biology Source Type: research

Abstract 4755: Estrogen receptor mediates novel mechanisms of estrogen-induced growth and tamoxifen resistance in invasive lobular carcinoma
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer representing ∼10% of newly diagnosed breast tumors. Over 90% of ILC cases are ER-positive, however, endocrine response and estrogen signaling are not well described in ILC. Retrospective analyses suggest that ILC patients treated with endocrine therapy have poorer outcomes than invasive ductal carcinoma (IDC) patients with similar biomarkers, and that ILC patients may not benefit from adjuvant tamoxifen. Additionally, we have recently identified ILC-specific ER-target genes and de novo tamoxifen resistance driven by ER in ILC model systems. Based...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Sikora, M. J., Bahreini, A., Oesterreich, S. Tags: Endocrinology Source Type: research

Abstract P3-04-05: Invasive lobular carcinoma cell lines utilize WNT4 signaling to mediate estrogen-induced growth
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer representing 10-15% of newly diagnosed breast tumors. Over 90% of ILC are ER-positive, however, endocrine response and estrogen signaling are not well described in ILC. Retrospective analyses suggest that ILC patients treated with endocrine therapy have poorer outcomes than similar invasive ductal carcinoma (IDC) patients, and that ILC patients may not benefit from adjuvant tamoxifen. Additionally, we recently identified ILC-specific ER-target genes and de novo tamoxifen resistance driven by ER in ILC model systems. Based on these observations, we ...
Source: Cancer Research - April 30, 2015 Category: Cancer & Oncology Authors: Sikora, M. J., Bahreini, A., Alexander, C. M., Oesterreich, S. Tags: Poster Session Abstracts Source Type: research

Abstract P3-04-02: Invasive lobular carcinoma cell lines utilize WNT4 signaling to mediate estrogen-induced growth
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer representing 10-15% of newly diagnosed breast tumors. Over 90% of ILC are estrogen receptor (ER)-positive, however, endocrine response and estrogen signaling are not well understood in ILC. Retrospective analyses suggest that ILC patients treated with endocrine therapy have poorer outcomes than invasive ductal carcinoma (IDC) patients, and that ILC patients may not benefit from adjuvant tamoxifen. Based on these observations, we hypothesize that ER regulates unique signaling pathways in ILC cells that control growth and endocrine response.To identi...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Sikora, M., Oesterreich, S. Tags: Poster Session Abstracts Source Type: research