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Differential Roles of AKT Isoforms in Metastatic Prostate Cancer.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Differential Roles of AKT Isoforms in Metastatic Prostate Cancer./
作者:	Miller, Karina A.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
面頁冊數:	136 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-12, Section: B.
Contained By:	Dissertations Abstracts International81-12B.
標題:	Biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27964545
ISBN:	9798617073326

Differential Roles of AKT Isoforms in Metastatic Prostate Cancer.
Miller, Karina A.

Differential Roles of AKT Isoforms in Metastatic Prostate Cancer. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 136 p.

Source: Dissertations Abstracts International, Volume: 81-12, Section: B.

Thesis (Ph.D.)--State University of New York at Buffalo, 2020.

This item must not be sold to any third party vendors.

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.

ISBN: 9798617073326Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

Genetics

Differential Roles of AKT Isoforms in Metastatic Prostate Cancer.
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520 $a 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.
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