{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86482"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86482","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Differential Roles of AKT Isoforms in Metastatic Prostate Cancer","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Miller, Karina; 0000-0001-7684-9746"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gelman, Irwin","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T17:22:52Z","date_published":"2025-02-21T17:22:52Z","updated_at":"2026-07-27T19:05:32Z","subjects":["biology","cellular biology","genetics"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86482","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gelman, Irwin","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Miller, Karina; 0000-0001-7684-9746"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T17:22:52Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["biology","cellular biology","genetics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86482"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","The present study was designed to dissect the molecular mechanisms that drive prostate cancer (CaP) metastatic aggressiveness. Specifically, this work addresses how specific AKT isoform members, part of the PI3K/AKT pathway, drive metastatic CaP progression, and how PTEN, a PI3K/AKT signaling antagonist that is highly mutated in CaP, controls disease progression by modulating dependence on particular AKT isoforms. This thesis work started as an attempt to dissect an enigma from two transgenic mouse models of CaP, both with activated AKT yet dramatically different phenotypes. The loss of PTEN function, one of the most frequent mutations in CaP, is presumed to drive disease progression through activation of PI3K/AKT signaling. However, two transgenic mouse CaP models that genocopy changes found in human CaP, Pten/Rb-loss and Akap12/Rb-loss, differ in their disease aggressiveness even though both exhibit Akt activation and loss of Rb: Pten/Rb-deficient mice develop aggressive prostate adenocarcinomas and systemic metastasis, while Akap12/Rb-deficient mice develop high-grade prostatic intraepithelial neoplasias (HG-PIN) and early dissemination of prostate cells to local lymph nodes. Additionally, the HG-PIN lesions showed upregulation of Smad4, a gene thought to function as a metastasis suppressor. Previous studies have suggested that AKT isoforms have opposing roles in malignant progression. Parsing AKT isoform-preferential functions in these transgenic models would therefore provide mechanistic insights into CaP biologies related to metastasis: chemotaxis and metastatic invasiveness, survival during anchorage-independent growth, and proliferation, as well as assist in identifying upstream PI3K isoform targets for cancer therapy with higher precision.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Differential Roles of AKT Isoforms in Metastatic Prostate Cancer"]}]}],"canonical_facts":{"dc:contributor":["Gelman, Irwin","Roswell Park"],"dc:creator":["Miller, Karina; 0000-0001-7684-9746"],"dc:date":["2025-02-21T17:22:52Z","2020"],"dc:description":["Ph.D.","The present study was designed to dissect the molecular mechanisms that drive prostate cancer (CaP) metastatic aggressiveness. Specifically, this work addresses how specific AKT isoform members, part of the PI3K/AKT pathway, drive metastatic CaP progression, and how PTEN, a PI3K/AKT signaling antagonist that is highly mutated in CaP, controls disease progression by modulating dependence on particular AKT isoforms. This thesis work started as an attempt to dissect an enigma from two transgenic mouse models of CaP, both with activated AKT yet dramatically different phenotypes. The loss of PTEN function, one of the most frequent mutations in CaP, is presumed to drive disease progression through activation of PI3K/AKT signaling. However, two transgenic mouse CaP models that genocopy changes found in human CaP, Pten/Rb-loss and Akap12/Rb-loss, differ in their disease aggressiveness even though both exhibit Akt activation and loss of Rb: Pten/Rb-deficient mice develop aggressive prostate adenocarcinomas and systemic metastasis, while Akap12/Rb-deficient mice develop high-grade prostatic intraepithelial neoplasias (HG-PIN) and early dissemination of prostate cells to local lymph nodes. Additionally, the HG-PIN lesions showed upregulation of Smad4, a gene thought to function as a metastasis suppressor. Previous studies have suggested that AKT isoforms have opposing roles in malignant progression. Parsing AKT isoform-preferential functions in these transgenic models would therefore provide mechanistic insights into CaP biologies related to metastasis: chemotaxis and metastatic invasiveness, survival during anchorage-independent growth, and proliferation, as well as assist in identifying upstream PI3K isoform targets for cancer therapy with higher precision.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86482"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["biology","cellular biology","genetics"],"dc:title":["Differential Roles of AKT Isoforms in Metastatic Prostate Cancer"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:32Z"}