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Regulation of apoptosis by the Bcl-2...

Rothermund, Christy Ann.

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Regulation of apoptosis by the Bcl-2 family of proteins in the LNCaP prostate cancer cell line progression model.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Regulation of apoptosis by the Bcl-2 family of proteins in the LNCaP prostate cancer cell line progression model./
作者:	Rothermund, Christy Ann.
面頁冊數:	185 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-06, Section: B, page: 2526.
Contained By:	Dissertation Abstracts International64-06B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3093286

Regulation of apoptosis by the Bcl-2 family of proteins in the LNCaP prostate cancer cell line progression model.
Rothermund, Christy Ann.

Regulation of apoptosis by the Bcl-2 family of proteins in the LNCaP prostate cancer cell line progression model. - 185 p.

Source: Dissertation Abstracts International, Volume: 64-06, Section: B, page: 2526.

Thesis (Ph.D.)--University of Nebraska Medical Center, 2003.

The highly conserved process of apoptosis plays a critical role in development and cellular homeostasis. Deregulated apoptosis has been shown to protect cancer cells from death signals, which make the study of apoptosis regulation an attractive target for therapeutic intervention. The goal of these studies was to determine the nature of apoptosis deregulation that leads to the androgen-independent phenotype in prostate cancer. The LNCaP prostate cancer cell line undergoes genetic and phenotypic changes upon continuous passage <italic>in vitro</italic>, including development of androgen-independence. The high-passage, androgen-unresponsive (LNCaP-UR) cells exhibit increased resistance to the induction of apoptosis when compared to low-passage, androgen-responsive (LNCaP-R) cells. Analysis of apoptosis regulators during LNCaP progression to androgen-unresponsiveness revealed that Bcl-2 protein was not detected in LNCaP-UR cells. Perturbation of androgen-signaling by growth of cells in serum-depleted conditions resulted in detectable Bcl-2 protein expression in LNCaP-UR cells, and LNCaP-R cells appeared to overexpress Bcl-2. Treatment of LNCaP-R cells with the non-steroidal antiandrogen, casodex, resulted in downregulation of Bcl-2 protein levels, indicating regulation of Bcl-2 protein expression by androgen signaling. Exogenous expression of a histidine-tagged Bcl-2 construct in the LNCaP-UR cells showed reduced cross-reactivity to anti-Bcl-2 antibodies suggesting a possible modification of the Bcl-2 protein. The modification did not appear to be phosphorylation since a phosphorylated form of Bcl-2 could be detected in LNCaP-R cells. Bcl-2 was not turned over via the ubiquitin-proteasome pathway or degraded via the calpain proteolytic pathway in either LNCaP-R or UR cells. DNA microarray analysis was performed to identify genes that may potentially regulate Bcl-2 and be responsible for the androgen-insensitive, apoptotic resistance of these cells. The data showed genes regulated by hypoxia, including the Bcl-2 interacting protein BNIP3, were overexpressed in LNCaP cells after treatment with casodex. The results of these studies show that apoptosis is deregulated in the LNCaP prostate cancer progression model and this deregulation may be responsible for the androgen-independent progression of prostate cancer.Subjects--Topical Terms:

1017686
Biology, Cell.

Regulation of apoptosis by the Bcl-2 family of proteins in the LNCaP prostate cancer cell line progression model.
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520 $a The highly conserved process of apoptosis plays a critical role in development and cellular homeostasis. Deregulated apoptosis has been shown to protect cancer cells from death signals, which make the study of apoptosis regulation an attractive target for therapeutic intervention. The goal of these studies was to determine the nature of apoptosis deregulation that leads to the androgen-independent phenotype in prostate cancer. The LNCaP prostate cancer cell line undergoes genetic and phenotypic changes upon continuous passage <italic>in vitro</italic>, including development of androgen-independence. The high-passage, androgen-unresponsive (LNCaP-UR) cells exhibit increased resistance to the induction of apoptosis when compared to low-passage, androgen-responsive (LNCaP-R) cells. Analysis of apoptosis regulators during LNCaP progression to androgen-unresponsiveness revealed that Bcl-2 protein was not detected in LNCaP-UR cells. Perturbation of androgen-signaling by growth of cells in serum-depleted conditions resulted in detectable Bcl-2 protein expression in LNCaP-UR cells, and LNCaP-R cells appeared to overexpress Bcl-2. Treatment of LNCaP-R cells with the non-steroidal antiandrogen, casodex, resulted in downregulation of Bcl-2 protein levels, indicating regulation of Bcl-2 protein expression by androgen signaling. Exogenous expression of a histidine-tagged Bcl-2 construct in the LNCaP-UR cells showed reduced cross-reactivity to anti-Bcl-2 antibodies suggesting a possible modification of the Bcl-2 protein. The modification did not appear to be phosphorylation since a phosphorylated form of Bcl-2 could be detected in LNCaP-R cells. Bcl-2 was not turned over via the ubiquitin-proteasome pathway or degraded via the calpain proteolytic pathway in either LNCaP-R or UR cells. DNA microarray analysis was performed to identify genes that may potentially regulate Bcl-2 and be responsible for the androgen-insensitive, apoptotic resistance of these cells. The data showed genes regulated by hypoxia, including the Bcl-2 interacting protein BNIP3, were overexpressed in LNCaP cells after treatment with casodex. The results of these studies show that apoptosis is deregulated in the LNCaP prostate cancer progression model and this deregulation may be responsible for the androgen-independent progression of prostate cancer.
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