Nuclear factor-κB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate

Christopher Sweeney, Lang Li, Rajasubramaniam Shanmugam, Poornima Bhat-Nakshatri, Vetrichelvan Jayaprakasan, Lee Ann Baldridge, Thomas Gardner, Martin Smith, Harikrishna Nakshatri, Liang Cheng

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Purpose: The transcription factor nuclear factor-κB (NF-κB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. Experimental Design: Electromobility gel shift assays were used to evaluate NF-κB DNA binding in vitro. The functional relevance of NF-κB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-κB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-κB subunit was used to determine the frequency and location of NF-κB in 97 prostatectomy specimens. The amount of staining was quantified on a 0-3+ scale. Results: An electromobility gel shift assay confirmed the presence of NFκB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-κB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage. Conclusions: NF-κB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-κB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-κB for the prevention and/or treatment of prostate cancer.

Original languageEnglish
Pages (from-to)5501-5507
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number16
DOIs
StatePublished - Aug 15 2004

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Prostatic Intraepithelial Neoplasia
Prostate
Prostatic Neoplasms
Staining and Labeling
Prostatectomy
DNA
Epithelium
Gels
Immunohistochemistry
Oligonucleotide Array Sequence Analysis
Adenocarcinoma in Situ
In Vitro Techniques
Neoplasms
Carcinogenesis
Research Design
Transcription Factors
Cell Line
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Nuclear factor-κB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate. / Sweeney, Christopher; Li, Lang; Shanmugam, Rajasubramaniam; Bhat-Nakshatri, Poornima; Jayaprakasan, Vetrichelvan; Baldridge, Lee Ann; Gardner, Thomas; Smith, Martin; Nakshatri, Harikrishna; Cheng, Liang.

In: Clinical Cancer Research, Vol. 10, No. 16, 15.08.2004, p. 5501-5507.

Research output: Contribution to journalArticle

Sweeney, Christopher ; Li, Lang ; Shanmugam, Rajasubramaniam ; Bhat-Nakshatri, Poornima ; Jayaprakasan, Vetrichelvan ; Baldridge, Lee Ann ; Gardner, Thomas ; Smith, Martin ; Nakshatri, Harikrishna ; Cheng, Liang. / Nuclear factor-κB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 16. pp. 5501-5507.
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abstract = "Purpose: The transcription factor nuclear factor-κB (NF-κB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. Experimental Design: Electromobility gel shift assays were used to evaluate NF-κB DNA binding in vitro. The functional relevance of NF-κB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-κB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-κB subunit was used to determine the frequency and location of NF-κB in 97 prostatectomy specimens. The amount of staining was quantified on a 0-3+ scale. Results: An electromobility gel shift assay confirmed the presence of NFκB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-κB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70{\%}, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage. Conclusions: NF-κB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-κB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-κB for the prevention and/or treatment of prostate cancer.",
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T1 - Nuclear factor-κB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate

AU - Sweeney, Christopher

AU - Li, Lang

AU - Shanmugam, Rajasubramaniam

AU - Bhat-Nakshatri, Poornima

AU - Jayaprakasan, Vetrichelvan

AU - Baldridge, Lee Ann

AU - Gardner, Thomas

AU - Smith, Martin

AU - Nakshatri, Harikrishna

AU - Cheng, Liang

PY - 2004/8/15

Y1 - 2004/8/15

N2 - Purpose: The transcription factor nuclear factor-κB (NF-κB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. Experimental Design: Electromobility gel shift assays were used to evaluate NF-κB DNA binding in vitro. The functional relevance of NF-κB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-κB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-κB subunit was used to determine the frequency and location of NF-κB in 97 prostatectomy specimens. The amount of staining was quantified on a 0-3+ scale. Results: An electromobility gel shift assay confirmed the presence of NFκB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-κB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage. Conclusions: NF-κB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-κB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-κB for the prevention and/or treatment of prostate cancer.

AB - Purpose: The transcription factor nuclear factor-κB (NF-κB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. Experimental Design: Electromobility gel shift assays were used to evaluate NF-κB DNA binding in vitro. The functional relevance of NF-κB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-κB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-κB subunit was used to determine the frequency and location of NF-κB in 97 prostatectomy specimens. The amount of staining was quantified on a 0-3+ scale. Results: An electromobility gel shift assay confirmed the presence of NFκB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-κB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage. Conclusions: NF-κB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-κB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-κB for the prevention and/or treatment of prostate cancer.

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