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Involvement of beta-catenin mutation...

Chesire, Dennis Robert.

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Involvement of beta-catenin mutation and nuclear signaling in prostate cancer.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Involvement of beta-catenin mutation and nuclear signaling in prostate cancer./
Author:	Chesire, Dennis Robert.
Description:	166 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0499.
Contained By:	Dissertation Abstracts International64-02B.
Subject:	Biology, Cell. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3080639

Involvement of beta-catenin mutation and nuclear signaling in prostate cancer.
Chesire, Dennis Robert.

Involvement of beta-catenin mutation and nuclear signaling in prostate cancer. - 166 p.

Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0499.

Thesis (Ph.D.)--The Johns Hopkins University, 2003.

Understanding the molecular mechanisms responsible for prostate cancer (CaP) development and progression is paramount for overcoming two major problems confronting clinicians: a lack of reliable prognostic markers for rational disease management (1) and a limited, usually inadequate armamentarium for blocking progression of advanced lesions (2). Always with the aim to provide insights that may ultimately aid future endeavors to successfully tackle these obstacles, this thesis was carried out to address the role of beta-catenin signaling in CaP, particularly that which is associated with aberrant beta-catenin post-translational regulation. beta-catenin serves as both a structural component in adherens junctions and as a nuclear signaling molecule, the latter function of which has been shown to effect wnt/wingless pathway activity and to be implicated in the oncogenesis of several human cancers. Herein, in vivo evidence garnered from mutation and immunohistological analyses is presented detailing the potential involvement of beta-catenin activation and nuclear accumulation in certain subsets of human prostate tumors. Although there is considerable lack of comprehension regarding the function of presumptive beta-catenin transcriptional activity in these tumors, our in vitro data (luciferase assays) indicate the likelihood that its signaling via transactivation of T cell factor (TCF) transcription factors does occur and is subject to input from other pathways for which a causative role in CaP is already known. Androgen receptor (AR) signaling is the most notable among these pathways: ligand-dependent AR function represses beta-catenin/TCF target gene expression, whilst beta-catenin and TCF over-expression enhances and inhibits AR transcriptional activity, respectively. Although the exact mechanisms for these "distinct" forms of AR/beta-catenin/TCF pathway cross-talk remain elusive, important features of each cross-regulatory event have hinted towards working models thereof. In total, my thesis has uncovered certain avenues through which beta-catenin may exert its CaP-related function, as well as its normal signaling function in the prostate; indeed, future experimentation is necessary to test the veracity of these signaling data, and their phenotypic effects, within a more in vivo setting. Heightening our comprehension of beta-catenin signaling in CaP should provide greater understanding of this disease and could eventually prove useful in developing more effective anti-tumor therapies.Subjects--Topical Terms:

1017686
Biology, Cell.

Involvement of beta-catenin mutation and nuclear signaling in prostate cancer.
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245 1 0 $a Involvement of beta-catenin mutation and nuclear signaling in prostate cancer.
300 $a 166 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-02, Section: B, page: 0499.
500 $a Adviser: William B. Isaacs.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2003.
520 $a Understanding the molecular mechanisms responsible for prostate cancer (CaP) development and progression is paramount for overcoming two major problems confronting clinicians: a lack of reliable prognostic markers for rational disease management (1) and a limited, usually inadequate armamentarium for blocking progression of advanced lesions (2). Always with the aim to provide insights that may ultimately aid future endeavors to successfully tackle these obstacles, this thesis was carried out to address the role of beta-catenin signaling in CaP, particularly that which is associated with aberrant beta-catenin post-translational regulation. beta-catenin serves as both a structural component in adherens junctions and as a nuclear signaling molecule, the latter function of which has been shown to effect wnt/wingless pathway activity and to be implicated in the oncogenesis of several human cancers. Herein, in vivo evidence garnered from mutation and immunohistological analyses is presented detailing the potential involvement of beta-catenin activation and nuclear accumulation in certain subsets of human prostate tumors. Although there is considerable lack of comprehension regarding the function of presumptive beta-catenin transcriptional activity in these tumors, our in vitro data (luciferase assays) indicate the likelihood that its signaling via transactivation of T cell factor (TCF) transcription factors does occur and is subject to input from other pathways for which a causative role in CaP is already known. Androgen receptor (AR) signaling is the most notable among these pathways: ligand-dependent AR function represses beta-catenin/TCF target gene expression, whilst beta-catenin and TCF over-expression enhances and inhibits AR transcriptional activity, respectively. Although the exact mechanisms for these "distinct" forms of AR/beta-catenin/TCF pathway cross-talk remain elusive, important features of each cross-regulatory event have hinted towards working models thereof. In total, my thesis has uncovered certain avenues through which beta-catenin may exert its CaP-related function, as well as its normal signaling function in the prostate; indeed, future experimentation is necessary to test the veracity of these signaling data, and their phenotypic effects, within a more in vivo setting. Heightening our comprehension of beta-catenin signaling in CaP should provide greater understanding of this disease and could eventually prove useful in developing more effective anti-tumor therapies.
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792 $a 2003
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