2012
DOI: 10.1158/0008-5472.can-12-1119
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Regulation of ERBB2 Receptor by t-DARPP Mediates Trastuzumab Resistance in Human Esophageal Adenocarcinoma

Abstract: Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor outcome. Although targeting ERBB2 with trastuzumab is evaluated in clinical trials, the molecular mechanisms of trastuzumab resistance remain uncharacterized in EAC. The dopamine and cyclic AMP-regulated phosphoprotein of Mr 32,000 (DARPP-32), also known as PPP1R1B, is located together with ERBB2 at the 17q12-q21 amplicon. We evaluated the expression of a transcript variant of DARPP-32 (t-DARPP) and ERBB2 in 141 primary tumors and investig… Show more

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Cited by 44 publications
(55 citation statements)
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“…2b), respectively. In the case of trastuzumab, our results are in line with the data from Hong et al [23].…”
Section: Expression Of Gli-1 and Ihh In Human Esophageal Adenocarcinosupporting
confidence: 93%
“…2b), respectively. In the case of trastuzumab, our results are in line with the data from Hong et al [23].…”
Section: Expression Of Gli-1 and Ihh In Human Esophageal Adenocarcinosupporting
confidence: 93%
“…Blots are representative of 2 independent experiments. C and D, Akt stability in the presence of 100M CHX in SFM was assessed by measuring Akt levels by immunoblot at different time points of incubation in SFM (h) as described (28) in (C) sortilin-overexpressing and (D) progranulindepleted PC3 cells. Blots are representative of 2 independent experiments.…”
Section: Discussionmentioning
confidence: 99%
“…Akt stability was assessed as described (28). Briefly, cells were seeded into 6-well plates in serum-containing medium.…”
Section: Cycloheximide (Chx)-based Akt Protein Stability Assaymentioning
confidence: 99%
“…Several other mutations involving the PI3K pathway, PIK3CA codon 600, PTEN codon By contrast, substantially less effort has been devoted to investigating the means of intrinsic or acquired resistance to trastuzumab and other ERBB2-targeting agents in GE adenocarcinomas. Based on cell line models, activation of the cAMP-regulated phosphoprotein t-DARPP (25) and the kinase SRC (16) has been shown to mediate acquired resistance to trastuzumab. However, it is not known which pathways are responsible for the de novo or intrinsic resistance that many ERBB2-positive patients demonstrate with ERBB2-directed therapy.…”
Section: Introductionmentioning
confidence: 99%