Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult.

Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Research Abstract Details 

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Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Abstract Text:

Janet K Hess-Wilson,Hannah K Daly,William A Zagorski,Christopher P Montville,Karen E Knudsen,

Prostate cancer cells are dependent on androgen for growth and survival; as such, inhibition of androgen receptor (AR) activity is the first line of intervention for disseminated disease. Recently, specific cytotoxic agents have been shown to extend survival times in patients with advanced disease. Given the established ability of androgen to modify cell survival in prostate cancer cells, it is imperative to determine the effect of the hormonal environment on cytotoxic response. Here, we show that the response of prostate cancer cells to taxane-induced cell death is significantly enhanced by androgen stimulation in AR-positive, androgen-dependent prostate cancer cells. Similar results were observed on androgen-independent AR activation. By contrast, AR-positive yet androgen-independent or AR-negative cells were refractory to androgen influence on taxane function. The ability of androgen to potentiate taxane activity was dependent on its mitogenic capacity and was separable from overall AR activity, as coadministration of AR antagonists, G(1) cyclin-dependent kinase inhibitors, or high-dose (growth inhibitory) androgen nullified the proapoptotic function of androgen. Observed induction of cell death was attributed to caspase-dependent apoptosis and correlated with p53 activation. Combined, these data indicate that the cytotoxic effects of taxanes are substantially influenced by the hormonal environment and/or status of AR activity in prostate cancer cells and provide the foundation for refinement and optimization of cytotoxic intervention in prostate cancer.

Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Publishing Authors By Initials

JK Hess-Wilson,HK Daly,WA Zagorski,CP Montville,KE Knudsen,

For similar organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, alicyclic: cycloparaffins: cyclodecanes: taxoids research abstracts see: organic chemicals: hydrocarbons: hydrocarbons, cyclic: hydrocarbons, alicyclic: cycloparaffins: cyclodecanes: taxoids research

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Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer research

VOLUME: 66

Page Numbers: 11998-2008

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 15

MONTH: Dec

YEAR: 2006

Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Keywords Mesh Terms:

KEYWORDS: Taxoids

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult. Information

Substance Name: Prostate-Specific Antigen

Registry Number: EC 3.4.21.77

Grant and Affiliation Information for Mitogenic action of the androgen receptor sensitizes prostate cancer cells to taxane-based cytotoxic insult.

AFFILIATION: Department of Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01-CA 93404

ACRONYM: CA

MEDLINETA: Cancer Res

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