000			nab a22 7a 4500
999			_c17339 _d17339
003			PC17339
005			20230328115909.0
008			230327b xxu||||| |||| 00| 0 eng d
040			_cH12O
041			_aeng
100			_92951 _aPérez Gómez, Eduardo _eInstituto de Investigación imas12
100			_92950 _aAndradas, Clara _eInstituto de Investigación imas12
100			_92952 _aBlasco Benito, Sandra _eInstituto de Investigación imas12
100			_93236 _aCaffarel, María M _eInstituto de Investigación imas12
100			_93237 _aGarcía Taboada, Elena _eInstituto de Investigación imas12
100			_93235 _aGuzmán, Manuel _eInstituto de Investigación imas12
100			_92953 _aSánchez, Cristina _eInstituto de Investigación imas12
245	0	0	_aRole of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer. _h[artículo]
260			_bJournal of the National Cancer Institute, _c2015
300			_a107(6):djv077.
500			_aFormato Vancouver: Pérez Gómez E, Andradas C, Blasco Benito S, Caffarel MM, García Taboada E, Villa Morales M et al. Role of cannabinoid receptor CB2 in HER2 pro-oncogenic signaling in breast cancer. J Natl Cancer Inst. 2015 Apr 8;107(6):djv077.
501			_aPMID: 25855725
504			_aContiene 55 referencias
520			_aBackground: Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown. Methods: We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen, and Freiburg between 1997 and 2010 and CB2 mRNA expression in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2) rat ortholog (neu) and lacks CB2 and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by colocalization, coimmunoprecipitation, and proximity ligation assays. Statistical tests were two-sided. Results: We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis (decreased overall survival, hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.09 to 0.71, P = .009) and higher probability to suffer local recurrence (HR = 0.09, 95% CI = 0.049 to 0.54, P = .003) and to develop distant metastases (HR = 0.33, 95% CI = 0.13 to 0.75, P = .009). We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade and that an increased CB2 expression activates the HER2 pro-oncogenic signaling at the level of the tyrosine kinase c-SRC. Finally, we show HER2 and CB2 form heteromers in cancer cells. Conclusions: Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with prognostic value in these tumors.
710			_9625 _aInstituto de Investigación imas12
856			_uhttp://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc17339.pdf _ySolicitar documento
942			_2ddc _cART _n0