Mostrar el registro sencillo del ítem
dc.contributor.author
Gattelli, Albana
dc.contributor.author
Garcia Sola, Martin Emilio
dc.contributor.author
Roloff, Tim C.
dc.contributor.author
Cardiff, Robert D.
dc.contributor.author
Kordon, Edith Claudia
dc.contributor.author
Chodosh, Lewis A.
dc.contributor.author
Hynes, Nancy E.
dc.date.available
2022-10-05T12:01:09Z
dc.date.issued
2018-07
dc.identifier.citation
Gattelli, Albana; Garcia Sola, Martin Emilio; Roloff, Tim C.; Cardiff, Robert D.; Kordon, Edith Claudia; et al.; Chronic expression of wild-type Ret receptor in the mammary gland induces luminal tumors that are sensitive to Ret inhibition; Nature Publishing Group; Oncogene; 37; 29; 7-2018; 4046-4054
dc.identifier.issn
0950-9232
dc.identifier.uri
http://hdl.handle.net/11336/171880
dc.description.abstract
The receptor tyrosine kinase Ret, a key gain-of-function mutated oncoprotein in thyroid carcinomas, has recently been implicated in other cancer types. While Ret copy number gains and mutations have been reported at low frequencies in breast tumors, we and others have reported that Ret is overexpressed in about 40% of human tumors and this correlates with poor patient prognosis. Ret activation regulates numerous intracellular pathways related to proliferation and inflammation, but it is not known whether abnormal Ret expression is sufficient to induce mammary carcinomas. Using a novel doxycycline-inducible transgenic mouse model with the MMTV promoter controlling Ret expression, we show that overexpression of wild-type Ret in the mammary epithelium produces mammary tumors, displaying a morphology that recapitulates characteristics of human luminal breast tumors. Ret-evoked tumors are estrogen receptor positive and negative for progesterone receptor. Moreover, tumors rapidly regress after doxycycline withdrawal, indicating that Ret is the driving oncoprotein. Using next-generation sequencing, we examined the levels of transcripts in these tumors, confirming a luminal signature. Ret-evoked tumors have been passaged in mice and used to test novel therapeutic approaches. Importantly, we have determined that tumors are resistant to endocrine therapy, but respond successfully to treatment with a Ret kinase inhibitor. Our data provide the first compelling evidence for an oncogenic role of non-mutated Ret in the mammary gland and are an incentive for clinical development of Ret as a cancer biomarker and therapeutic target.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Mammary gland
dc.subject
Breast Cancer
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Chronic expression of wild-type Ret receptor in the mammary gland induces luminal tumors that are sensitive to Ret inhibition
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-04-20T14:48:28Z
dc.journal.volume
37
dc.journal.number
29
dc.journal.pagination
4046-4054
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Gattelli, Albana. Friedrich Miescher Institute For Biomedical Research; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Garcia Sola, Martin Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Roloff, Tim C.. Friedrich Miescher Institute For Biomedical Research; Suiza
dc.description.fil
Fil: Cardiff, Robert D.. University of California at Davis; Estados Unidos
dc.description.fil
Fil: Kordon, Edith Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
dc.description.fil
Fil: Chodosh, Lewis A.. University of California at Davis; Estados Unidos
dc.description.fil
Fil: Hynes, Nancy E.. Friedrich Miescher Institute For Biomedical Research; Suiza. Universidad de Basilea; Suiza
dc.journal.title
Oncogene
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41388-018-0235-y
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/s41388-018-0235-y
Archivos asociados