The Role of Hedgehog Gene During Prostatic Tumorigenesis

博士 === 中山醫學大學 === 生化暨生物科技研究所 === 95 === With little knowledge about the origin and development of androgen-independent prostate cancer, no effective therapy has been available so far. Recently, a cancer stem/progenitor cell hypothesis has been proposed, in which abnormal prostatic basal cells or the...

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Main Authors: Bo-Yie, 陳伯易
Other Authors: David Pei-Cheng Lin
Format: Others
Language:zh-TW
Published: 2007
Online Access:http://ndltd.ncl.edu.tw/handle/28332669482452415122
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spelling ndltd-TW-095CSMU51070382015-10-28T04:07:07Z http://ndltd.ncl.edu.tw/handle/28332669482452415122 The Role of Hedgehog Gene During Prostatic Tumorigenesis Hedgehog基因在前列腺癌發生過程所扮演角色之探討 Bo-Yie 陳伯易 博士 中山醫學大學 生化暨生物科技研究所 95 With little knowledge about the origin and development of androgen-independent prostate cancer, no effective therapy has been available so far. Recently, a cancer stem/progenitor cell hypothesis has been proposed, in which abnormal prostatic basal cells or their progeny cells are regarded as the cause of malignant androgen- independent tumorigenesis. Hedgehog (Hh) gene is thought to be reactivated during self-renewal and differentiation of adult stem cells, leading to tissue regeneration or cancer stem cells activation. Recent studies have implicated hyperactive Hh signaling in advanced and metastatic prostate cancers, but the molecular mechanism of Hh involved in prostate tumorigenesis remains unclear. In this study, we addressed the effects of Hh overexpression by intraprostate injection of an Hh-expressing vector. The manipulation, with confirmed Hh signaling pathway activation, caused lesions originated from prostatic basal cells showing characteristic PIN or invasive CaP phenotypes. Further analyses demonstrated Hh involvement in heterogeneous basal cell lineage differentiation, AR-negative cancer formation, cancer stem cell activation, cell proliferation, and metastasis. Furthermore, we indicated Hedgehog involvement in forming BCH and its progressing towards CaP in human prostate cancer, presumably by transforming the normal basal stem cells into the cancer stem cells where persistent Hedgehog activation might be mandatory for tumorigenesis. To conclude, a mouse prostate cancer model induced by Hh-overexpression was established and may be used for testing novel therapeutical approaches targeting at Hh signaling pathway. David Pei-Cheng Lin Jer-Yuh Liu 林培正 劉哲育 2007 學位論文 ; thesis 98 zh-TW
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language zh-TW
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description 博士 === 中山醫學大學 === 生化暨生物科技研究所 === 95 === With little knowledge about the origin and development of androgen-independent prostate cancer, no effective therapy has been available so far. Recently, a cancer stem/progenitor cell hypothesis has been proposed, in which abnormal prostatic basal cells or their progeny cells are regarded as the cause of malignant androgen- independent tumorigenesis. Hedgehog (Hh) gene is thought to be reactivated during self-renewal and differentiation of adult stem cells, leading to tissue regeneration or cancer stem cells activation. Recent studies have implicated hyperactive Hh signaling in advanced and metastatic prostate cancers, but the molecular mechanism of Hh involved in prostate tumorigenesis remains unclear. In this study, we addressed the effects of Hh overexpression by intraprostate injection of an Hh-expressing vector. The manipulation, with confirmed Hh signaling pathway activation, caused lesions originated from prostatic basal cells showing characteristic PIN or invasive CaP phenotypes. Further analyses demonstrated Hh involvement in heterogeneous basal cell lineage differentiation, AR-negative cancer formation, cancer stem cell activation, cell proliferation, and metastasis. Furthermore, we indicated Hedgehog involvement in forming BCH and its progressing towards CaP in human prostate cancer, presumably by transforming the normal basal stem cells into the cancer stem cells where persistent Hedgehog activation might be mandatory for tumorigenesis. To conclude, a mouse prostate cancer model induced by Hh-overexpression was established and may be used for testing novel therapeutical approaches targeting at Hh signaling pathway.
author2 David Pei-Cheng Lin
author_facet David Pei-Cheng Lin
Bo-Yie
陳伯易
author Bo-Yie
陳伯易
spellingShingle Bo-Yie
陳伯易
The Role of Hedgehog Gene During Prostatic Tumorigenesis
author_sort Bo-Yie
title The Role of Hedgehog Gene During Prostatic Tumorigenesis
title_short The Role of Hedgehog Gene During Prostatic Tumorigenesis
title_full The Role of Hedgehog Gene During Prostatic Tumorigenesis
title_fullStr The Role of Hedgehog Gene During Prostatic Tumorigenesis
title_full_unstemmed The Role of Hedgehog Gene During Prostatic Tumorigenesis
title_sort role of hedgehog gene during prostatic tumorigenesis
publishDate 2007
url http://ndltd.ncl.edu.tw/handle/28332669482452415122
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