The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression.

The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Research Abstract Details 

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The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Abstract Text:

Meletios Verras,Jane Lee,Hui Xue,Tzu-Huey Li,Yuzhuo Wang,Zijie Sun,

The precise molecular mechanisms by which prostate cancer cells progress from androgen-sensitive to androgen-insensitive status still remain largely unclear. The hepatocyte growth factor/scatter factor (HGF/SF) plays a critical role in the regulation of cell growth, cell motility, morphogenesis, and angiogenesis. The aberrant expression of HGF/SF and its receptor, c-Met, often correlates with poor prognosis in a variety of human malignancies, including prostate cancer. Here, we investigate a potential link between androgen signaling and c-Met expression in prostate cancer cells. First, we showed that the androgen receptor (AR) represses the expression of c-Met in a ligand-dependent manner. Using different c-Met promoter/reporter constructs, we identified that Sp1 induces the transcription of c-Met and that AR can repress the Sp1-induced transcription in prostate cancer cells. Moreover, the data from electrophoretic mobility shift assay showed that AR interferes with the interaction between Sp1 and the functional Sp1 binding site within the c-Met promoter. Furthermore, we tested the effect of AR on c-Met expression in an androgen-insensitive prostate cancer cell line, CWR22Rv1. Finally, the repressive role of androgen signaling on c-Met expression was confirmed in prostate cancer xenografts. The above data indicate a dual role of AR in transcriptional regulation. Although the current androgen ablation therapy can repress the expression of growth-promoting genes that are activated by the AR, it may also attenuate the repressive role of AR on c-Met expression. Therefore, the therapeutic strategies to inhibit the activation of the HGF/c-Met pathway may be of benefit when combined with current androgen ablation treatment.

The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Publishing Authors By Initials

M Verras,J Lee,H Xue,TH Li,Y Wang,Z Sun,

For similar surgical procedures, operative: transplantation: transplantation, heterologous research abstracts see: surgical procedures, operative: transplantation: transplantation, heterologous research

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The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Journal Published:

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

Journal: Cancer research

VOLUME: 67

Page Numbers: 967-75

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Feb

YEAR: 2007

The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Keywords Mesh Terms:

KEYWORDS: Transplantation, Heterologous

MESH TERMS: metabolism

Chemical & Substance for Abstract: The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression. Information

Substance Name: Proto-Oncogene Proteins c-met

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for The androgen receptor negatively regulates the expression of c-Met: implications for a novel mechanism of prostate cancer progression.

AFFILIATION: Departments of Urology and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK 61002

ACRONYM: DK

MEDLINETA: Cancer Res

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