Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells.

Adenoviral-mediated expression of MMAC/PTEN inhibits proliferation and metastasis of human prostate cancer cells.
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发表时间：
2002-06
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
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通讯作者：
M. Davies;S. J. Kim;N. Parikh;Z. Dong;C. Bucana;G. Gallick
M. Davies;S. J. Kim;N. Parikh;Z. Dong;C. Bucana;G. Gallick
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其他
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作者：
M. Davies;S. J. Kim;N. Parikh;Z. Dong;C. Bucana;G. Gallick

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目的本研究的目的是确定MM​​AC/PTEN的腺病毒转基因表达对PC3人前列腺癌细胞的体外和体内生长和存活的影响。实验设计将表达MMAC/PTEN或绿色荧光蛋白的腺病毒作为对照引入PC3细胞中，并确定对原位裸鼠模型中信号转导途径和肿瘤生长的影响。结果 PC3 细胞中 MMAC/PTEN 的表达降低了磷酸 Akt 的水平，但不降低磷酸 Mapk 或 FAK 的水平。 MMAC/PTEN 的表达主要通过阻断细胞周期进程来抑制 PC3 细胞的体外生长。离体引入MMAC/PTEN表达并不能抑制原位植入的PC3细胞的致瘤性，但它确实显着减小了肿瘤大小并完全抑制了转移的形成。用腺病毒 MMAC/PTEN 体内治疗预先建立的原位 PC3 肿瘤并没有显着减小局部肿瘤大小，但确实减少了转移形成。结论 MMAC/PTEN 在体内模型系统中功能性调节前列腺癌细胞转移潜能，可能是人类前列腺癌的重要生物标志物和治疗靶点。
PURPOSE The purpose of this study was to determine the effects of adenoviral transgene expression of MMAC/PTEN on the in vitro and in vivo growth and survival of PC3 human prostate cancer cells. EXPERIMENTAL DESIGN Adenoviruses expressing MMAC/PTEN or green fluorescent protein as a control were introduced into PC3 cells, and effects on signal transduction pathways and growth of tumors in an orthotopic nude mouse model were determined. RESULTS MMAC/PTEN expression in PC3 cells decreased the level of phospho Akt but not that of phospho Mapk or FAK. Expression of MMAC/PTEN inhibited the in vitro growth of PC3 cells primarily by blocking cell cycle progression. Ex vivo introduction of MMAC/PTEN expression did not inhibit the tumorigenicity of orthotopically implanted PC3 cells, but it did significantly reduce tumor size and completely inhibited the formation of metastases. In vivo treatment of pre-established orthotopic PC3 tumors with adenoviral MMAC/PTEN did not significantly reduce local tumor size, but it did diminish metastasis formation. CONCLUSIONS MMAC/PTEN functionally regulates prostate cancer cell metastatic potential in an in vivo model system and may be an important biological marker and therapeutic target for human prostate cancer.