Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential
RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is presen...
| Autores: | ; ; ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artigo |
| Estado: | Published version |
| Data de publicação: | 2022 |
| País: | Argentina |
| Recursos: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositório: | CONICET Digital (CONICET) |
| Idioma: | Inglês |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/214634 |
| Acesso em linha: | http://hdl.handle.net/11336/214634 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | RET Mammary tumors STAT Involution https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| _version_ | 1878403607223599104 |
|---|---|
| author | Vallone, Sabrina Aldana |
| author2 | Garcia Sola, Martin Emilio Schere Levy, Carolina Paula Meiss, Roberto P. Hermida, Gladys Noemí Chodosh, Lewis A. Kordon, Edith Claudia Hynes, Nancy E. Gattelli, Albana |
| author2_role | author author author author author author author author |
| author_browse | Chodosh, Lewis A. Garcia Sola, Martin Emilio Gattelli, Albana Hermida, Gladys Noemí Hynes, Nancy E. Kordon, Edith Claudia Meiss, Roberto P. Schere Levy, Carolina Paula Vallone, Sabrina Aldana |
| author_facet | Vallone, Sabrina Aldana Garcia Sola, Martin Emilio Schere Levy, Carolina Paula Meiss, Roberto P. Hermida, Gladys Noemí Chodosh, Lewis A. Kordon, Edith Claudia Hynes, Nancy E. Gattelli, Albana |
| author_role | author |
| collection | CONICET Digital (CONICET) |
| description | RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA-seq, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | AR_9e7e0c740eaf5fcb0befd6e21ee43f4d |
| identifier_str_mv | Vallone, Sabrina Aldana; Garcia Sola, Martin Emilio; Schere Levy, Carolina Paula; Meiss, Roberto P.; Hermida, Gladys Noemí; et al.; Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential; Company of Biologists; Disease Models And Mechanisms; 15; 3; 3-2022; 1-14 1754-8403 1754-8411 CONICET Digital CONICET |
| institution | Consejo Nacional de Investigaciones Científicas y Técnicas |
| instname_str | Consejo Nacional de Investigaciones Científicas y Técnicas |
| language | eng |
| network_acronym_str | AR |
| network_name_str | Argentina |
| oai_identifier_str | oai:ri.conicet.gov.ar:11336/214634 |
| publishDate | 2022 |
| publishDateSort | 2022 |
| publisher | Company of Biologists |
| publisherStr | Company of Biologists |
| reponame_str | CONICET Digital (CONICET) |
| spelling | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential Vallone, Sabrina Aldana Garcia Sola, Martin Emilio Schere Levy, Carolina Paula Meiss, Roberto P. Hermida, Gladys Noemí Chodosh, Lewis A. Kordon, Edith Claudia Hynes, Nancy E. Gattelli, Albana RET Mammary tumors STAT Involution https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 RET is a receptor tyrosine kinase with oncogenic potential in the mammary epithelium. Several receptors with oncogenic activity in the breast are known to participate in specific developmental stages. We found that RET is differentially expressed during mouse mammary gland development: RET is present in lactation and its expression dramatically decreases in involution, the period during which the lactating gland returns to a quiescent state after weaning. Based on epidemiological and pre-clinical findings, involution has been described as tumor promoting. Using the Ret/MTB doxycycline-inducible mouse transgenic system we show that sustained expression of RET in the mammary epithelium during the post-lactation transition to involution is accompanied by alterations in tissue remodeling and an enhancement of cancer potential. Following constitutive Ret expression we observed a significant increase in neoplastic lesions in the post-involuting versus the virgin mammary gland. Furthermore, we show that abnormal RET overexpression during lactation promotes factors that prime involution, including premature activation of Stat3 signaling and, using RNA-seq, an acute-phase inflammatory signature. Our results demonstrate that RET overexpression negatively affects the normal post-lactation transition. Fil: Vallone, Sabrina Aldana. 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 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 Fil: Schere Levy, Carolina Paula. 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 Fil: Meiss, Roberto P.. Academia Nacional de Medicina de Buenos Aires; Argentina Fil: Hermida, Gladys Noemí. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina Fil: Chodosh, Lewis A.. University of Pennsylvania; Estados Unidos 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 Fil: Hynes, Nancy E.. Friedrich Miescher Institute For Biomedical Research; Suiza Fil: Gattelli, Albana. 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 Company of Biologists http://hdl.handle.net/11336/214634 Vallone, Sabrina Aldana; Garcia Sola, Martin Emilio; Schere Levy, Carolina Paula; Meiss, Roberto P.; Hermida, Gladys Noemí; et al.; Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential; Company of Biologists; Disease Models And Mechanisms; 15; 3; 3-2022; 1-14 1754-8403 1754-8411 CONICET Digital CONICET |
| spellingShingle | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential Vallone, Sabrina Aldana RET Mammary tumors STAT Involution https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| status_str | publishedVersion |
| title | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential |
| title_full | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential |
| title_fullStr | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential |
| title_full_unstemmed | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential |
| title_short | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential |
| title_sort | Aberrant RET expression impacts on normal mammary gland post-lactation transition enhancing cancer potential |
| topic | RET Mammary tumors STAT Involution https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| topic_facet | RET Mammary tumors STAT Involution https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
| url | http://hdl.handle.net/11336/214634 |