{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:44:42Z","timestamp":1791143082096,"version":"4.1.0"},"reference-count":35,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":6188,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["mp.uscap.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Modern Pathology"],"published-print":{"date-parts":[[2006,2]]},"DOI":"10.1038\/modpathol.3800525","type":"journal-article","created":{"date-parts":[[2005,12,9]],"date-time":"2005-12-09T11:05:37Z","timestamp":1134126337000},"page":"238-245","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":153,"title":["The Akt pathway in human breast cancer: a tissue-array-based analysis"],"prefix":"10.1016","volume":"19","author":[{"given":"Shikha","family":"Bose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sindhu","family":"Chandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M","family":"Mirocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namrata","family":"Bose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1038\/modpathol.3800525_bib1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrc839","article-title":"The phosphatidylinositol 3-kinase AKT pathway in human cancer","volume":"2","author":"Vivanco","year":"2002","journal-title":"Nat Rev Cancer"},{"key":"10.1038\/modpathol.3800525_bib2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S1535-6108(03)00248-4","article-title":"Targeting the PI3K-Akt pathway in human cancer: rationale and promise","volume":"4","author":"Luo","year":"2003","journal-title":"Cancer Cell"},{"key":"10.1038\/modpathol.3800525_bib3","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrc1362","article-title":"The TOR pathway: a target for cancer therapy","volume":"4","author":"Bjornsti","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"10.1038\/modpathol.3800525_bib4","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0960-7404(03)00004-5","article-title":"A decade of tyrosine kinases: from gene discovery to therapeutics","volume":"12","author":"Craven","year":"2003","journal-title":"Surg Oncol"},{"key":"10.1038\/modpathol.3800525_bib5","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1023\/A:1006806722619","article-title":"The IRS-signalling system: a network of docking proteins that mediate insulin action","volume":"182","author":"White","year":"1998","journal-title":"Mol Cell Biochem"},{"key":"10.1038\/modpathol.3800525_bib6","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/S0960-9822(00)00728-4","article-title":"Expression of the pro-apoptotic Bcl-2 family member Bim is regulated by the forkhead transcription factor FKHR-L1","volume":"10","author":"Dijkers","year":"2000","journal-title":"Curr Biol"},{"issue":"Part 2","key":"10.1038\/modpathol.3800525_bib7","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1042\/bj3440427","article-title":"Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation","volume":"344","author":"Nave","year":"1999","journal-title":"Biochem J"},{"key":"10.1038\/modpathol.3800525_bib8","doi-asserted-by":"crossref","first-page":"3499","DOI":"10.1101\/gad.12.22.3499","article-title":"Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization","volume":"12","author":"Diehl","year":"1998","journal-title":"Genes Dev"},{"key":"10.1038\/modpathol.3800525_bib9","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1126\/science.275.5308.1943","article-title":"PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer","volume":"275","author":"Li","year":"1997","journal-title":"Science"},{"key":"10.1038\/modpathol.3800525_bib10","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0092-8674(00)81780-8","article-title":"Negative regulation of PKB\/Akt-dependent cell survival by the tumor suppressor PTEN","volume":"95","author":"Stambolic","year":"1998","journal-title":"Cell"},{"key":"10.1038\/modpathol.3800525_bib11","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.1073\/pnas.84.14.5034","article-title":"Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma","volume":"84","author":"Staal","year":"1987","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/modpathol.3800525_bib12","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1073\/pnas.93.8.3636","article-title":"Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA","volume":"93","author":"Cheng","year":"1996","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/modpathol.3800525_bib13","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1038\/sj.onc.1203597","article-title":"PIK3CA as an oncogene in cervical cancer","volume":"19","author":"Ma","year":"2000","journal-title":"Oncogene"},{"key":"10.1038\/modpathol.3800525_bib14","first-page":"7426","article-title":"The phosphatidylinositol 3\u2032-kinase p85alpha gene is an oncogene in human ovarian and colon tumors","volume":"61","author":"Philp","year":"2001","journal-title":"Cancer Res"},{"key":"10.1038\/modpathol.3800525_bib15","doi-asserted-by":"crossref","first-page":"772","DOI":"10.4161\/cbt.3.8.994","article-title":"The PIK3CA gene is mutated with high frequency in human breast cancers","volume":"3","author":"Bachman","year":"2004","journal-title":"Cancer Biol Ther"},{"key":"10.1038\/modpathol.3800525_bib16","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1093\/jnci\/92.11.924","article-title":"Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers","volume":"92","author":"Mutter","year":"2000","journal-title":"J Natl Cancer Inst"},{"key":"10.1038\/modpathol.3800525_bib17","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1053\/hupa.2002.124721","article-title":"Reduced expression of PTEN correlates with breast cancer progression","volume":"33","author":"Bose","year":"2002","journal-title":"Hum Pathol"},{"key":"10.1038\/modpathol.3800525_bib18","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ccr.2004.06.022","article-title":"PTEN activation contributes to tumor inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients","volume":"6","author":"Nagata","year":"2004","journal-title":"Cancer Cell"},{"key":"10.1038\/modpathol.3800525_bib19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/sj.onc.1201940","article-title":"Allelic loss of chromosome 10q23 is associated with invasion in breast carcinomas","volume":"17","author":"Bose","year":"1998","journal-title":"Oncogene"},{"key":"10.1038\/modpathol.3800525_bib20","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/jnci\/91.22.1922","article-title":"Mutational spectra of PTEN\/MMAC1 gene: a tumor suppressor with lipid phosphatase activity","volume":"91","author":"Ali","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"10.1038\/modpathol.3800525_bib21","first-page":"1904","article-title":"Adenoviral-mediated expression of MMAC\/PTEN inhibits proliferation and metastasis of human prostate cancer cells","volume":"8","author":"Davies","year":"2002","journal-title":"Clin Cancer Res"},{"key":"10.1038\/modpathol.3800525_bib22","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0304-3835(01)00632-2","article-title":"Suppression of tumorigenicity and metastasis in B16F10 cells by PTEN\/MMAC1\/TEP1 gene","volume":"172","author":"Hwang","year":"2001","journal-title":"Cancer Lett"},{"key":"10.1038\/modpathol.3800525_bib23","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1038\/sj.onc.1208368","article-title":"Loss of the tumor suppressor gene PTEN marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive germ cell tumors","volume":"24","author":"Di Vizio","year":"2005","journal-title":"Oncogene"},{"key":"10.1038\/modpathol.3800525_bib24","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1126\/science.280.5369.1614","article-title":"Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN","volume":"280","author":"Tamura","year":"1998","journal-title":"Science"},{"key":"10.1038\/modpathol.3800525_bib25","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/path.1611","article-title":"The role of PTEN and its signalling pathways, including AKT, in breast cancer; an assessment of relationships with other prognostic factors and with outcome","volume":"204","author":"Panigrahi","year":"2004","journal-title":"J Pathol"},{"key":"10.1038\/modpathol.3800525_bib26","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0960-9822(00)00417-6","article-title":"Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases","volume":"10","author":"Liliental","year":"2000","journal-title":"Curr Biol"},{"key":"10.1038\/modpathol.3800525_bib27","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/S0092-8674(02)00663-3","article-title":"P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac","volume":"108","author":"Welch","year":"2002","journal-title":"Cell"},{"key":"10.1038\/modpathol.3800525_bib28","doi-asserted-by":"crossref","first-page":"6779","DOI":"10.1158\/1078-0432.CCR-04-0112","article-title":"Activation of the Akt\/mammalian target of rapamycin\/4E-BP1 pathway by ErbB2 overexpression predicts tumor progression in breast cancers","volume":"10","author":"Zhou","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1038\/modpathol.3800525_bib29","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1073\/pnas.98.1.136","article-title":"A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt","volume":"98","author":"Aoki","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1038\/modpathol.3800525_bib30","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1038\/sj.onc.1207550","article-title":"An essential role for protein synthesis in oncogenic cellular transformation","volume":"23","author":"Bader","year":"2004","journal-title":"Oncogene"},{"key":"10.1038\/modpathol.3800525_bib31","doi-asserted-by":"crossref","first-page":"8059","DOI":"10.1158\/1078-0432.CCR-04-0035","article-title":"Inhibition of mTOR activity restores tamoxifen response in breast cancer cells with aberrant Akt Activity","volume":"10","author":"deGraffenried","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1038\/modpathol.3800525_bib32","doi-asserted-by":"crossref","first-page":"8351","DOI":"10.1158\/1078-0432.CCR-04-0130","article-title":"Antibody-based profiling of the phosphoinositide 3-kinase pathway in clinical prostate cancer","volume":"10","author":"Thomas","year":"2004","journal-title":"Clin Cancer Res"},{"key":"10.1038\/modpathol.3800525_bib33","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/(SICI)1098-2264(199805)22:1<66::AID-GCC9>3.0.CO;2-5","article-title":"Mechanism of cyclin D1 (CCND1, PRAD1) overexpression in human cancer cells: analysis of allele-specific expression","volume":"22","author":"Hosokawa","year":"1998","journal-title":"Genes Chromosomes Cancer"},{"key":"10.1038\/modpathol.3800525_bib34","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/(SICI)1097-4644(1996)25+<23::AID-JCB3>3.0.CO;2-4","article-title":"Relevance of cyclin D1 and other molecular markers to cancer chemoprevention","volume":"25","author":"Weinstein","year":"1996","journal-title":"J Cell Biochem Suppl"},{"key":"10.1038\/modpathol.3800525_bib35","first-page":"141","article-title":"Cyclin D1 expression and patient outcome after tamoxifen therapy in estrogen receptor positive metastatic breast cancer","volume":"10","author":"Han","year":"2003","journal-title":"Oncol Rep"}],"container-title":["Modern Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/3800525.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/3800525","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0893395222019974?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0893395222019974?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/3800525.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T00:55:54Z","timestamp":1760230554000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0893395222019974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2]]},"references-count":35,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,2]]}},"alternative-id":["S0893395222019974"],"URL":"https:\/\/doi.org\/10.1038\/modpathol.3800525","relation":{},"ISSN":["0893-3952"],"issn-type":[{"value":"0893-3952","type":"print"}],"subject":[],"published":{"date-parts":[[2006,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The Akt pathway in human breast cancer: a tissue-array-based analysis","name":"articletitle","label":"Article Title"},{"value":"Modern Pathology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1038\/modpathol.3800525","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2006 United States & Canadian Academy of Pathology.","name":"copyright","label":"Copyright"}]}}