FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2029822832> ?p ?o ?g. }

• W2029822832 endingPage "ii37" @default.
• W2029822832 startingPage "ii37" @default.
• W2029822832 abstract "ABSTRACT Endocrine resistance is a major clinical issue. AP-1 is a transcription factor downstream of different growth factor receptors (GFR) and stress-related signaling cascades implicated in endocrine resistance. We have previously shown that acquired endocrine resistance is associated with increased AP-1 activity. Moreover, AP-1 modulates the estrogen receptor (ER) transcriptional program, especially upon high GFR signaling. We therefore hypothesized that interfering with AP-1 could circumvent endocrine resistance. Methods and results AP-1 was genetically inhibited by siRNA or by stable expression of an inducible dominant-negative (DN) c-Jun in MCF7 cells. In vitro, siRNA c-Jun significantly inhibited the growth of acquired tamoxifen resistant (TamR) MCF7 derivatives (>95% inhibition, p = .001) but not of parental cells (p = .06). Xenografts of two inducible DN c-Jun clones were established in nude mice. Mice were randomized to continued estrogen (E2) supplementation or to either estrogen deprivation (ED) or Tam, all in the presence or absence of DN c-Jun. AP-1 blockade significantly reduced time to tumor response (p = .014 and p = .006 for the two clones) and time to tumor disappearance (p = .001 and p = .0034) in the Tam group, with similar results in the ED group. In addition, AP-1 blockade significantly delayed TamR by increasing time to tumor doubling (p = .002). Furthermore, induction of DN c-Jun resulted in dramatic tumor shrinkage after long-term Tam treatment, suggesting reversal of endocrine resistance with AP-1 blockade. Interestingly, no significant effect was observed on E2-stimulated tumor growth. Immunohystochemistry showed that AP-1 blockade reduced proliferation and induced apoptosis. A gene signature of our TamR MCF7 xenografts significantly overlapped (p  Conclusions We show that AP-1 blockade increases tumor sensitivity and circumvents resistance to endocrine therapy. We suggest that AP-1 is critical in a switch in the ER transcriptional program and may be a new hallmark of endocrine resistance. Disclosure All authors have declared no conflicts of interest." @default.
• W2029822832 created "2016-06-24" @default.
• W2029822832 creator A5000472972 @default.
• W2029822832 creator A5000497626 @default.
• W2029822832 creator A5001231739 @default.
• W2029822832 creator A5001666750 @default.
• W2029822832 creator A5001814176 @default.
• W2029822832 creator A5003301011 @default.
• W2029822832 creator A5004938979 @default.
• W2029822832 creator A5005191627 @default.
• W2029822832 creator A5005795874 @default.
• W2029822832 creator A5007897192 @default.
• W2029822832 creator A5007900716 @default.
• W2029822832 creator A5008381160 @default.
• W2029822832 creator A5012603842 @default.
• W2029822832 creator A5012798032 @default.
• W2029822832 creator A5016024325 @default.
• W2029822832 creator A5016057308 @default.
• W2029822832 creator A5016363044 @default.
• W2029822832 creator A5016791239 @default.
• W2029822832 creator A5018688642 @default.
• W2029822832 creator A5018736882 @default.
• W2029822832 creator A5018738617 @default.
• W2029822832 creator A5019736223 @default.
• W2029822832 creator A5020374002 @default.
• W2029822832 creator A5020510548 @default.
• W2029822832 creator A5020548005 @default.
• W2029822832 creator A5021145156 @default.
• W2029822832 creator A5021327528 @default.
• W2029822832 creator A5021685638 @default.
• W2029822832 creator A5021851232 @default.
• W2029822832 creator A5022012288 @default.
• W2029822832 creator A5022513362 @default.
• W2029822832 creator A5024692757 @default.
• W2029822832 creator A5025550778 @default.
• W2029822832 creator A5027651565 @default.
• W2029822832 creator A5027879987 @default.
• W2029822832 creator A5027914471 @default.
• W2029822832 creator A5029930673 @default.
• W2029822832 creator A5030115311 @default.
• W2029822832 creator A5030928151 @default.
• W2029822832 creator A5034058277 @default.
• W2029822832 creator A5036009351 @default.
• W2029822832 creator A5037248394 @default.
• W2029822832 creator A5037340510 @default.
• W2029822832 creator A5037461394 @default.
• W2029822832 creator A5037977357 @default.
• W2029822832 creator A5038334067 @default.
• W2029822832 creator A5038428719 @default.
• W2029822832 creator A5038884410 @default.
• W2029822832 creator A5039958127 @default.
• W2029822832 creator A5040775339 @default.
• W2029822832 creator A5041459747 @default.
• W2029822832 creator A5041495974 @default.
• W2029822832 creator A5043546858 @default.
• W2029822832 creator A5044589772 @default.
• W2029822832 creator A5044689386 @default.
• W2029822832 creator A5044880752 @default.
• W2029822832 creator A5048648579 @default.
• W2029822832 creator A5049425681 @default.
• W2029822832 creator A5050057356 @default.
• W2029822832 creator A5050990881 @default.
• W2029822832 creator A5051135936 @default.
• W2029822832 creator A5051138792 @default.
• W2029822832 creator A5051359251 @default.
• W2029822832 creator A5052099734 @default.
• W2029822832 creator A5052648400 @default.
• W2029822832 creator A5053398622 @default.
• W2029822832 creator A5054103832 @default.
• W2029822832 creator A5054272532 @default.
• W2029822832 creator A5054610146 @default.
• W2029822832 creator A5054741652 @default.
• W2029822832 creator A5055005629 @default.
• W2029822832 creator A5055239489 @default.
• W2029822832 creator A5055450638 @default.
• W2029822832 creator A5055758268 @default.
• W2029822832 creator A5059808072 @default.
• W2029822832 creator A5060032419 @default.
• W2029822832 creator A5061642774 @default.
• W2029822832 creator A5062328139 @default.
• W2029822832 creator A5063001812 @default.
• W2029822832 creator A5063856184 @default.
• W2029822832 creator A5065482599 @default.
• W2029822832 creator A5066098323 @default.
• W2029822832 creator A5066110533 @default.
• W2029822832 creator A5066294430 @default.
• W2029822832 creator A5066313509 @default.
• W2029822832 creator A5066950401 @default.
• W2029822832 creator A5067974928 @default.
• W2029822832 creator A5068603135 @default.
• W2029822832 creator A5070149281 @default.
• W2029822832 creator A5070972824 @default.
• W2029822832 creator A5071535344 @default.
• W2029822832 creator A5072041322 @default.
• W2029822832 creator A5073398031 @default.
• W2029822832 creator A5073464070 @default.
• W2029822832 creator A5074117573 @default.
• W2029822832 creator A5076508834 @default.

• next