دورية أكاديمية
Elevated expression of wildtype RhoC promotes ErbB2- and Pik3ca-induced mammary tumor formation.
| العنوان: | Elevated expression of wildtype RhoC promotes ErbB2- and Pik3ca-induced mammary tumor formation. |
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| المؤلفون: | Raghuram N; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada.; Department of Molecular Genetics, The University of Toronto, Toronto, ON, M5S 1A8, Canada., Temel EI; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada.; Department of Molecular Genetics, The University of Toronto, Toronto, ON, M5S 1A8, Canada., Kawamata T; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada., Kozma KJ; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada.; Department of Molecular Genetics, The University of Toronto, Toronto, ON, M5S 1A8, Canada., Loch AJ; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada., Wang W; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada., Adams JR; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada., Muller WJ; Department of Biochemistry and Department of Medicine, Rosalind and Morris Goodman Cancer Research Institute, McGill University, Montreal, QC, H3A 1A3, Canada., Egan SE; Program in Cell Biology, The Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, 686 Bay Street, Room 16-9703, Toronto, ON, M5G 0A4, Canada. segan@sickkids.ca.; Department of Molecular Genetics, The University of Toronto, Toronto, ON, M5S 1A8, Canada. segan@sickkids.ca. |
| المصدر: | Breast cancer research : BCR [Breast Cancer Res] 2024 May 28; Vol. 26 (1), pp. 86. Date of Electronic Publication: 2024 May 28. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Ltd Country of Publication: England NLM ID: 100927353 Publication Model: Electronic Cited Medium: Internet ISSN: 1465-542X (Electronic) Linking ISSN: 14655411 NLM ISO Abbreviation: Breast Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: London, UK : BioMed Central Ltd Original Publication: London, UK : Current Science, c1999- |
| مواضيع طبية MeSH: | Receptor, ErbB-2*/metabolism , Receptor, ErbB-2*/genetics , rhoC GTP-Binding Protein*/metabolism , rhoC GTP-Binding Protein*/genetics , Class I Phosphatidylinositol 3-Kinases*/genetics , Class I Phosphatidylinositol 3-Kinases*/metabolism , Phosphatidylinositol 3-Kinases*/metabolism , Phosphatidylinositol 3-Kinases*/genetics , rho GTP-Binding Proteins*/metabolism , rho GTP-Binding Proteins*/genetics , Gene Expression Regulation, Neoplastic*, Animals ; Female ; Mice ; Humans ; Mice, Transgenic ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Mammary Neoplasms, Experimental/metabolism ; Epithelial-Mesenchymal Transition/genetics ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Breast Neoplasms/metabolism ; Signal Transduction |
| مستخلص: | Copy number gains in genes coding for Rho activating exchange factors as well as losses affecting genes coding for RhoGAP proteins are common in breast cancer (BC), suggesting that elevated Rho signaling may play an important role. Extra copies and overexpression of RHOC also occur, although a role for RhoC overexpression in driving tumor formation has not been assessed in vivo. To this end, we report on the development of a Rosa26 (R26)-targeted Cre-conditional RhoC overexpression mouse (R26 RhoC ). This mouse was crossed to two models for ERBB2/NEU + breast cancer: one based on expression of an oncogenic ErbB2/Neu cDNA downstream of the endogenous ErbB2 promoter (FloxNeoNeu NT ), the other, a metastatic model that is based on high-level expression from MMTV regulatory elements (NIC). RhoC overexpression dramatically enhanced mammary tumor formation in FloxNeoNeu NT mice but showed a more subtle effect in the NIC line, which forms multiple mammary tumors after a very short latency. RhoC overexpression also enhanced mammary tumor formation in an activated Pik3ca model for breast cancer (Pik3ca H1047R ). The transforming effect of RhoC was associated with epithelial/mesenchymal transition (EMT) in ErbB2/Neu NT and Pik3ca H1047R systems. Thus, our study reveals the importance of elevated wildtype Rho protein expression as a driver of breast tumor formation and highlights the significance of Copy Number Abberations that affect Rho signalling. (© 2024. The Author(s).) |
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| معلومات مُعتمدة: | 169023 Canadian Institute of Health Research; 169023 Canadian Institute of Health Research; 169023 Canadian Institute of Health Research; 169023 Canadian Institute of Health Research; 169023 Canadian Institute of Health Research; 169023 Canadian Institute of Health Research; 706353 Canadian Cancer Society Research Institute; 706353 Canadian Cancer Society Research Institute; 706353 Canadian Cancer Society Research Institute; 706353 Canadian Cancer Society Research Institute; 706353 Canadian Cancer Society Research Institute; 706353 Canadian Cancer Society Research Institute; 706353 Canadian Cancer Society Research Institute |
| المشرفين على المادة: | EC 2.7.10.1 (Receptor, ErbB-2) EC 3.6.5.2 (rhoC GTP-Binding Protein) EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 3.6.5.2 (rho GTP-Binding Proteins) EC 2.7.1.137 (Pik3ca protein, mouse) EC 2.7.10.1 (Erbb2 protein, mouse) EC 2.7.1.137 (PIK3CA protein, human) EC 3.6.5.2 (RHOC protein, human) |
| تواريخ الأحداث: | Date Created: 20240528 Date Completed: 20240529 Latest Revision: 20240531 |
| رمز التحديث: | 20240531 |
| مُعرف محوري في PubMed: | PMC11134842 |
| DOI: | 10.1186/s13058-024-01842-5 |
| PMID: | 38807216 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1465-542X |
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| DOI: | 10.1186/s13058-024-01842-5 |