{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:44:05Z","timestamp":1785908645067,"version":"3.56.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>\n                    Canine mammary tumor (CMT) represents the most frequently diagnosed neoplasm in intact female dogs and exhibits a high malignant rate. The PI3K\/AKT pathway critically drives tumor progression, and serves as a target for multiple anti-tumor drugs. In this study, two CMT cell lines (CHMp and CIPm) were employed to assess the impact of lentivirus-mediated PI3K over-expression. Functional assays were performed to evaluate proliferation, migration, and invasion capacities, as well as the expression levels of associated proteins. As a result, PI3K over-expressing cells exhibited a significantly increase in proliferation, migration, and invasion compared to cells in negative control (NC) group. Additionally, western blot analyses revealed that PI3K over-expression evoked concordant alterations in apoptosis-related proteins, including elevated phospho-AKT and Bcl-2 coupled with reduced Bax, implying that PI3K-mediated attenuation of apoptosis facilitated tumor progression. Moreover, results from tumor xenograft mouse model experiments indicated that PI3K over-expression significantly promotes tumor growth\n                    <jats:italic>in vivo<\/jats:italic>\n                    . The present study confirmed the function of PI3K in accelerating the growth and invasive capacity of CMT, laying an experimental foundation for the exploration of PI3K-targeted therapies.\n                  <\/jats:p>","DOI":"10.3389\/fvets.2026.1897100","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:46:30Z","timestamp":1785905190000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PI3K over-expression drives canine mammary tumor progression"],"prefix":"10.3389","volume":"13","author":[{"given":"Rong","family":"Chen","sequence":"first","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shipeng","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxin","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yana","family":"Li","sequence":"additional","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyan","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Animal Science, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]},{"name":"University Key Laboratory for Integrated Chinese Traditional and Western Veterinary Medicine and Animal Healthcare in Fujian Province","place":["Fuzhou, China"]},{"name":"Fujian Key Laboratory of Traditional Chinese Veterinary Medicine and Animal Health, Fujian Agriculture and Forestry University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1186\/s12917-022-03363-9","article-title":"Epidemiology of canine mammary tumours on the canary archipelago in Spain","volume":"18","author":"Rodr\u00edguez","year":"2022","journal-title":"BMC Vet Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"843390","DOI":"10.3389\/fvets.2022.843390","article-title":"Epidemiological investigation of canine mammary tumors in mainland China between 2017 and 2021","volume":"9","author":"Zheng","year":"2022","journal-title":"Front Vet Sci"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"5569","DOI":"10.1038\/s41598-024-56194-z","article-title":"Risk factor analysis and clinicopathological characteristics of female dogs with mammary tumours from a single-center retrospective study in Poland","volume":"14","author":"Dolka","year":"2024","journal-title":"Sci Rep"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2079","DOI":"10.3390\/ani11072079","article-title":"Dysregulation of PI3K\/Akt\/PTEN pathway in canine mammary tumor","volume":"11","author":"Kim","year":"2021","journal-title":"Animals"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.rvsc.2016.10.014","article-title":"Expression and activation of platelet-derived growth factor \u03b2 receptor, mitogen-activated protein\/extracellular signal-regulated kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) in canine mammary tumours","volume":"110","author":"Altamura","year":"2017","journal-title":"Res Vet Sci"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.18632\/oncotarget.26873","article-title":"P-cadherin mutations are associated with high basal Wnt activity and stemness in canine mammary tumor cell lines","volume":"10","author":"Timmermans-Sprang","year":"2019","journal-title":"Oncotarget"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s12272-024-01524-y","article-title":"Canine mammary tumors as a promising adjunct preclinical model for human breast cancer research: similarities, opportunities, and challenges","volume":"48","author":"Bhutta","year":"2025","journal-title":"Arch Pharm Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4048\/jbc.2023.26.e4","article-title":"Canine as a comparative and translational model for human mammary tumor","volume":"26","author":"Kwon","year":"2023","journal-title":"J Breast Cancer"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1177\/03009858231207021","article-title":"Review: the PI3K-AKT-mTOR signal transduction pathway in canine cancer","volume":"61","author":"Meuten","year":"2024","journal-title":"Vet Pathol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.jcpa.2023.08.007","article-title":"Activation of the Akt signalling pathway as a prognostic indicator in canine soft tissue sarcoma","volume":"206","author":"Miyanishi","year":"2023","journal-title":"J Comp Pathol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/1746-6148-8-73","article-title":"The class I PI3K\/Akt pathway is critical for cancer cell survival in dogs and offers an opportunity for therapeutic intervention","volume":"8","author":"Chen","year":"2012","journal-title":"BMC Vet Res"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e70295","DOI":"10.1002\/mco2.70295","article-title":"PI3K\/AKT\/mTOR Axis in Cancer: from pathogenesis to treatment","volume":"6","author":"Jiang","year":"2025","journal-title":"MedComm"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s43556-022-00110-2","article-title":"Targeting the PI3K\/AKT\/mTOR and RAF\/MEK\/ERK pathways for cancer therapy","volume":"3","author":"Li","year":"2022","journal-title":"Molecular Biomedicine"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1038\/s41419-020-02998-6","article-title":"PI3K\/AKT pathway as a key link modulates the multidrug resistance of cancers","volume":"11","author":"Liu","year":"2020","journal-title":"Cell Death Dis"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3390\/ijms26010145","article-title":"Dysregulated signaling pathways in canine mammary tumor and human triple negative breast Cancer: advances and potential therapeutic targets","volume":"26","author":"Mei","year":"2024","journal-title":"Int J Mol Sci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.gene.2019.02.076","article-title":"The relation between PI3K\/AKT signalling pathway and cancer","volume":"698","author":"Noorolyai","year":"2019","journal-title":"Gene"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.3390\/cells13171500","article-title":"PI3K\/AKT\/mTOR signaling network in human health and diseases","volume":"13","author":"Chamcheu","year":"2024","journal-title":"Cells"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"365","DOI":"10.3390\/ani11020365","article-title":"An Immunohistochemical study of the PTEN\/AKT pathway involvement in canine and feline mammary tumors","volume":"11","author":"Asproni","year":"2021","journal-title":"Animals"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.jconrel.2020.02.011","article-title":"Remodeling tumor immune microenvironment via targeted blockade of PI3K-\u03b3 and CSF-1\/CSF-1R pathways in tumor associated macrophages for pancreatic cancer therapy","volume":"321","author":"Li","year":"2020","journal-title":"J Control Release"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"101170","DOI":"10.1016\/j.drup.2024.101170","article-title":"Autophagy in cancer development, immune evasion, and drug resistance","volume":"78","author":"Niu","year":"2025","journal-title":"Drug Resist Updat"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e003402","DOI":"10.1136\/jitc-2021-003402","article-title":"PI3K activation allows immune evasion by promoting an inhibitory myeloid tumor microenvironment","volume":"10","author":"Collins","year":"2022","journal-title":"J Immunother Cancer"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"e2305922","DOI":"10.1002\/advs.202305922","article-title":"G3BP1 and SLU7 jointly promote immune evasion by downregulating MHC-I via PI3K\/Akt activation in bladder Cancer","volume":"11","author":"Zheng","year":"2024","journal-title":"Adv Sci"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1111\/vco.13005","article-title":"Auranofin suppresses the growth of canine mammary tumour cells and induces apoptosis via the PI3K\/AKT pathway","volume":"22","author":"Lin","year":"2024","journal-title":"Vet Comp Oncol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s12917-024-04085-w","article-title":"Establishment of canine mammary gland tumor cell lines harboring PI3K\/Akt activation as a therapeutic target","volume":"20","author":"Park","year":"2024","journal-title":"BMC Vet Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e23102","DOI":"10.1002\/jcla.23102","article-title":"The RAS-PI3K-AKT-NF-\u03baB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes and inhibits apoptosis in fibrous epulis","volume":"34","author":"Jiang","year":"2020","journal-title":"J Clin Lab Anal"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3892\/ijmm.2020.4781","article-title":"BCL2-regulated apoptotic process in myocardial ischemia-reperfusion injury (review)","volume":"47","author":"Korshunova","year":"2021","journal-title":"Int J Mol Med"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"21085","DOI":"10.1074\/jbc.M400063200","article-title":"Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils","volume":"279","author":"Gardai","year":"2004","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1002\/1873-3468.12030","article-title":"Regulation of Bax\/mitochondria interaction by AKT","volume":"590","author":"Simonyan","year":"2016","journal-title":"FEBS Lett"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"10781","DOI":"10.1074\/jbc.M500084200","article-title":"Nicotine inactivation of the proapoptotic function of Bax through phosphorylation","volume":"280","author":"Xin","year":"2005","journal-title":"J Biol Chem"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e45235","DOI":"10.15252\/embr.201745235","article-title":"Phosphorylation switches Bax from promoting to inhibiting apoptosis thereby increasing drug resistance","volume":"19","author":"Kale","year":"2018","journal-title":"EMBO Rep"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41419-025-07335-3","article-title":"Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma","volume":"16","author":"Kim","year":"2025","journal-title":"Cell Death Dis"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1007\/s10142-025-01693-z","article-title":"Hypoxia-induced S100A10 promotes glioblastoma malignancy and chemoresistance by activating PI3K-AKT signaling pathway","volume":"25","author":"Yang","year":"2025","journal-title":"Funct Integr Genomics"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.rvsc.2005.07.011","article-title":"Cyclopedic protein expression analysis of cultured canine mammary gland adenocarcinoma cells from six tumours","volume":"80","author":"Nakagawa","year":"2006","journal-title":"Res Vet Sci"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"e11","DOI":"10.1016\/j.jid.2016.11.020","article-title":"Research techniques made simple: analysis of collective cell migration using the wound healing assay","volume":"137","author":"Grada","year":"2017","journal-title":"J Invest Dermatol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/nrc3860","article-title":"PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting","volume":"15","author":"Thorpe","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"3949","DOI":"10.3390\/cancers13163949","article-title":"The pathogenic role of PI3K\/AKT pathway in Cancer onset and drug resistance","volume":"13","author":"Rascio","year":"2021","journal-title":"An Updated Review Cancers"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.semcancer.2021.06.019","article-title":"Attacking the PI3K\/Akt\/mTOR signaling pathway for targeted therapeutic treatment in human cancer","volume":"85","author":"Yu","year":"2022","journal-title":"Semin Cancer Biol"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s12943-023-01827-6","article-title":"PI3K\/AKT\/mTOR signaling transduction pathway and targeted therapies in cancer","volume":"22","author":"Glaviano","year":"2023","journal-title":"Mol Cancer"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1002\/mc.23467","article-title":"Lentiviral vector transduction provides nonspecific immunogenicity for syngeneic tumor models","volume":"61","author":"Bhuniya","year":"2022","journal-title":"Mol Carcinog"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.omtn.2022.05.029","article-title":"Antisense transcription from lentiviral gene targeting linked to an integrated stress response in colorectal cancer cells","volume":"28","author":"Ha","year":"2022","journal-title":"Molecular Therapy Nucleic Acids"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e0153069","DOI":"10.1371\/journal.pone.0153069","article-title":"Anti-apoptotic effects of lentiviral vector transduction promote increased rituximab tolerance in cancerous B-cells","volume":"11","author":"Ranjbar","year":"2016","journal-title":"PLoS One"}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1897100\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:46:34Z","timestamp":1785905194000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2026.1897100\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":42,"alternative-id":["10.3389\/fvets.2026.1897100"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2026.1897100","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]},"article-number":"1897100"}}