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Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein.

Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Research Abstract Details 

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  • Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Abstract Text:

    jocelyn c hsuJocelyn C Hsu,anurupa devAnurupa Dev,aimee wingAimee Wing,christine t brewChristine T Brew,leonard f bjeldanesLeonard F Bjeldanes,gary l firestoneGary L Firestone,

    Indole-3-carbinol (I3C), a dietary compound found naturally in cruciferous vegetables of the Brassica genus such as broccoli and brussels sprouts, induces a G1 growth arrest of human reproductive cancer cells. We previously reported that in LNCaP prostate cancer cells, I3C down-regulated cyclin-dependent kinase (CDK) 2 activity. In our current study, Western blotting and quantitative RT-PCR demonstrated that I3C treatment increased both the transcripts and protein levels of the CDK2 inhibitor p21(waf1/cip1) (p21). Transfection of luciferase reporter plasmids containing wild-type and mutated p21 promoter fragments revealed that I3C induced p21 gene transcription through a p53 DNA binding element. Oligonucleotide precipitation showed that I3C increased the level of activated p53 nuclear protein that is competent to bind its DNA target site on the p21 promoter. Ablation of p53 production using short interfering RNA (siRNA) prevented that the I3C induced G1 arrest and up-regulation of p21 expression. Western blots using p53 phospho-specific antibodies revealed that I3C treatment increased the levels of three phosphorylated forms of p53 (Ser15, Ser37, Ser392) that are known to contribute to p53 protein stability and greater transactivation potential. Taken together, our results establish that the I3C induced G1 arrest of human prostate cancer cells requires the induced production of the activated phosphorylated forms of p53, which stimulate transcription of the CDK2 inhibitor p21.

    Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Publishing Authors By Initials

    jc hsuJC Hsu,a devA Dev,a wingA Wing,ct brewCT Brew,lf bjeldanesLF Bjeldanes,gl firestoneGL Firestone,

    For similar genetic processes: gene expression regulation: up-regulation research abstracts see: genetic processes: gene expression regulation: up-regulation research

    PUBMED ID PMID:

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    Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Journal Published:

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

    Journal: Biochemical pharmacology

    VOLUME: 72

    Page Numbers: 1714-23

    Journal Abbreviation: Biochem. Pharmacol.

    ISSN: 0006-2952

    DAY: 12

    MONTH: 09

    YEAR: 2006

    Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 101032

    Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Keywords Mesh Terms:

    KEYWORDS: Up-Regulation

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein. Information

    Substance Name: Luciferases

    Registry Number: EC 1.13.12.-

    Grant and Affiliation Information for Indole-3-carbinol mediated cell cycle arrest of LNCaP human prostate cancer cells requires the induced production of activated p53 tumor suppressor protein.

    AFFILIATION: Department of Molecular and Cell Biology and The Cancer Research Laboratory, The University of California at Berkeley, Berkeley, CA 94720, USA.

    Country: England

    England Research PublicationEngland Research Publication

    AGENCY: United States NCI

    GRANT: CA102360

    ACRONYM: CA

    MEDLINETA: Biochem Pharmacol

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