FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1998367093> ?p ?o ?g. }

• W1998367093 abstract "Invasive lobular carcinoma (ILC) represents ∼10% of newly diagnosed breast tumors, accounting for ∼30,000 cases annually in the US. However, ILC has been understudied as a breast cancer subtype. ILC-specific signaling pathways and responses to endocrine therapies are not well characterized. Recent retrospective analyses of luminal-type breast cancers suggest that ILC patients treated with endocrine therapy have poorer disease-free survival and overall survival than invasive ductal carcinoma (IDC) patients with similar biomarkers. We hypothesize that unique transcriptional control of estrogen receptor-alpha (ERα) by estrogens and anti-estrogens in ILC cells drive a differential response of ILC tumors to endocrine therapies. The ILC cell lines MDA MB 134VI and SUM44PE were used as in vitro models of ILC tumors to examine responses to estradiol (E2) and the anti-estrogens tamoxifen (Tam), 4-hydroxytamoxifen (4OHT), endoxifen (Bx), and fulvestrant (ICI). We examined cell growth and expression of canonical ERα-regulated genes in response to E2. Cells were also treated with anti-estrogens +/− E2 to examine their ability to inhibit E2-induced growth. To establish a genome-wide profile of ERα-mediated gene regulation in ILC cells, ILC cells were subjected to gene expression microarray analysis following 0–24hrs treatment with 1nM E2. In parallel to these in vitro studies, in vivo models of ILC are being assessed for endocrine responsiveness, including MDA MB 134VI xenografts and the primary human tumor xenograft HCI-013. We observed that both MDA MB 134VI and SUM44PE are growth-induced by E2 treatment. However, both cell lines also present de novo resistance to Tam, 4OHT, and Bx. While ICI treatment completely blocked E2-induced growth in MDA MB 134VI, Tam, 4OHT, and Bx acted as partial agonists. Treatment with these compounds alone induced ∼25% growth relative to E2, and E2-induced growth could only be inhibited ∼75%. Similarly, SUM44PE cells are strongly growth-inhibited by ICI treatment, whereas growth is not reduced by Tam, 4OHT, or Bx treatment. Consistent with these observations, novel patterns of gene expression are induced by E2 treatment in ILC cells. E2-treatment induced canonical targets (e.g. GREB1, IGFBP4) in both ILC cell lines. However, in MDA MB 134VI cells only ∼35% of genes regulated by E2 at 24hrs overlap with those regulated in the IDC cell line MCF-7. Further, a subset of the overlapping genes is differentially regulated between cell types, including ESR1 (1.25-fold and 0.67-fold versus control in MDA MB 134VI and MCF-7, respectively), HOXC6, PMP22, and L1CAM. Examination of these observations in in vivo models is currently ongoing. These data are consistent with the hypothesis that E2 and anti-estrogens differentially regulate ERα-mediated gene expression in ILC cells versus IDC cells. The de novo resistance to tamoxifen observed in ILC cells may correlate with the worse outcomes in ILC patients observed in retrospective analyses. We hypothesize that elucidation of the mechanisms responsible for differential ERα regulation may reveal novel therapeutic targets for treating ILC patients and overcoming endocrine resistance. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-04-20." @default.
• W1998367093 created "2016-06-24" @default.
• W1998367093 creator A5022023149 @default.
• W1998367093 creator A5035665774 @default.
• W1998367093 creator A5047851862 @default.
• W1998367093 creator A5053026057 @default.
• W1998367093 creator A5055706123 @default.
• W1998367093 creator A5078571966 @default.
• W1998367093 date "2012-12-15" @default.
• W1998367093 modified "2023-09-26" @default.
• W1998367093 title "Abstract P6-04-20: Endocrine resistance in invasive lobular carcinoma cells parallels unique estrogen-mediated gene expression" @default.
• W1998367093 doi "https://doi.org/10.1158/0008-5472.sabcs12-p6-04-20" @default.
• W1998367093 hasPublicationYear "2012" @default.
• W1998367093 type Work @default.
• W1998367093 sameAs 1998367093 @default.
• W1998367093 citedByCount "0" @default.
• W1998367093 crossrefType "proceedings-article" @default.
• W1998367093 hasAuthorship W1998367093A5022023149 @default.
• W1998367093 hasAuthorship W1998367093A5035665774 @default.
• W1998367093 hasAuthorship W1998367093A5047851862 @default.
• W1998367093 hasAuthorship W1998367093A5053026057 @default.
• W1998367093 hasAuthorship W1998367093A5055706123 @default.
• W1998367093 hasAuthorship W1998367093A5078571966 @default.
• W1998367093 hasConcept C121608353 @default.
• W1998367093 hasConcept C126322002 @default.
• W1998367093 hasConcept C134018914 @default.
• W1998367093 hasConcept C143998085 @default.
• W1998367093 hasConcept C172313692 @default.
• W1998367093 hasConcept C2776166826 @default.
• W1998367093 hasConcept C2776372563 @default.
• W1998367093 hasConcept C2777164284 @default.
• W1998367093 hasConcept C2777176818 @default.
• W1998367093 hasConcept C2780482068 @default.
• W1998367093 hasConcept C3020375857 @default.
• W1998367093 hasConcept C46699223 @default.
• W1998367093 hasConcept C502942594 @default.
• W1998367093 hasConcept C530470458 @default.
• W1998367093 hasConcept C71315377 @default.
• W1998367093 hasConcept C71924100 @default.
• W1998367093 hasConcept C84606932 @default.
• W1998367093 hasConcept C86803240 @default.
• W1998367093 hasConceptScore W1998367093C121608353 @default.
• W1998367093 hasConceptScore W1998367093C126322002 @default.
• W1998367093 hasConceptScore W1998367093C134018914 @default.
• W1998367093 hasConceptScore W1998367093C143998085 @default.
• W1998367093 hasConceptScore W1998367093C172313692 @default.
• W1998367093 hasConceptScore W1998367093C2776166826 @default.
• W1998367093 hasConceptScore W1998367093C2776372563 @default.
• W1998367093 hasConceptScore W1998367093C2777164284 @default.
• W1998367093 hasConceptScore W1998367093C2777176818 @default.
• W1998367093 hasConceptScore W1998367093C2780482068 @default.
• W1998367093 hasConceptScore W1998367093C3020375857 @default.
• W1998367093 hasConceptScore W1998367093C46699223 @default.
• W1998367093 hasConceptScore W1998367093C502942594 @default.
• W1998367093 hasConceptScore W1998367093C530470458 @default.
• W1998367093 hasConceptScore W1998367093C71315377 @default.
• W1998367093 hasConceptScore W1998367093C71924100 @default.
• W1998367093 hasConceptScore W1998367093C84606932 @default.
• W1998367093 hasConceptScore W1998367093C86803240 @default.
• W1998367093 hasLocation W19983670931 @default.
• W1998367093 hasOpenAccess W1998367093 @default.
• W1998367093 hasPrimaryLocation W19983670931 @default.
• W1998367093 hasRelatedWork W1978315766 @default.
• W1998367093 hasRelatedWork W1989541937 @default.
• W1998367093 hasRelatedWork W1989693976 @default.
• W1998367093 hasRelatedWork W2006185042 @default.
• W1998367093 hasRelatedWork W2015023353 @default.
• W1998367093 hasRelatedWork W2041279175 @default.
• W1998367093 hasRelatedWork W2046640029 @default.
• W1998367093 hasRelatedWork W2070093834 @default.
• W1998367093 hasRelatedWork W2084405363 @default.
• W1998367093 hasRelatedWork W2093811845 @default.
• W1998367093 hasRelatedWork W2114007784 @default.
• W1998367093 hasRelatedWork W2334017319 @default.
• W1998367093 hasRelatedWork W248801835 @default.
• W1998367093 hasRelatedWork W2554626363 @default.
• W1998367093 hasRelatedWork W2564551512 @default.
• W1998367093 hasRelatedWork W2565295552 @default.
• W1998367093 hasRelatedWork W2768109071 @default.
• W1998367093 hasRelatedWork W2892236348 @default.
• W1998367093 hasRelatedWork W3039301238 @default.
• W1998367093 hasRelatedWork W3178965203 @default.
• W1998367093 isParatext "false" @default.
• W1998367093 isRetracted "false" @default.
• W1998367093 magId "1998367093" @default.
• W1998367093 workType "article" @default.