Protein tyrosine phosphorylation is a major posttranslational modification used by cells to regulate signal transduction and essentially participate in every aspect of cellular physiologic and pathogenic processes. Th...Protein tyrosine phosphorylation is a major posttranslational modification used by cells to regulate signal transduction and essentially participate in every aspect of cellular physiologic and pathogenic processes. The protein tyrosine phosphatase (PTP) super family of enzymes coordinately function with protein tyrosine kinases in signaling pathways that underlie a broad spectrum of fundamental physiological processes. Abnormal regulation of tyrosine phosphorylation or deregulation of phosphorylation is known to result in neoplastic or non-neoplastic diseases. Having evolved into separate families that are structurally and mechanistically distinct, PTPs have been implicated in a variety of diseases and efforts have been made to seek therapeutic clues from them. The phosphatases of regenerating liver (PRL) PRL-1, PRL-2, PRL-3 (also known as PTP4A1, PTP4A2, and PTP4A3, respectively) constitute a subfamily of the protein tyrosine phosphatases that have been suggested to play a key role in oncogenic and metastatic phenotypes.5 Here we review what is known about this novel class of small, prenylated phosphatases and its value in diagnosis and therapy of solid tumors.展开更多
目的:研究肝再生磷酸酶-3(phosphatase of regenerating liver,PRL-3)与鼻腔鼻窦鳞状细胞癌分化程度的关系,及其对鼻腔鼻窦鳞状细胞癌发病机制中的分子生物学作用,了解其相关性,从而使患者早期确诊,并对其预后的判断给予指导。方法:采...目的:研究肝再生磷酸酶-3(phosphatase of regenerating liver,PRL-3)与鼻腔鼻窦鳞状细胞癌分化程度的关系,及其对鼻腔鼻窦鳞状细胞癌发病机制中的分子生物学作用,了解其相关性,从而使患者早期确诊,并对其预后的判断给予指导。方法:采用免疫组化法对30例不同程度的鼻腔鼻窦鳞癌组织行PRL-3检测,并用20例鼻腔正常黏膜组织做为对照。结果:PRL-3在各级鼻腔鼻窦鳞癌组织中均有表达,与正常鼻黏膜比较有显著差异(P<0.05),随着鳞癌分级的升高其表达具有增强的趋势。结论:PRL-3在鼻腔鼻窦鳞状细胞癌中比在鼻息肉组织中表达显著增高,表明其可能与鼻腔鼻窦鳞癌的发生有关,可能是鳞癌发生的早期事件。展开更多
Background Considerable evidence suggests that phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in cancer metastasis; however, the molecular mechanisms remain largely unknown. The aim of this study w...Background Considerable evidence suggests that phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in cancer metastasis; however, the molecular mechanisms remain largely unknown. The aim of this study was to identify proteins associated with PRL-3-promoted colon cancer metastasis, by comparative proteomic analysis. Methods Proteomes of human colon cancer LoVo cells transfected with PRL-3 gene (LoVo-PRL-3) or empty vector PAcGFP-C3 (LoVo-control) were compared using 2D gel electrophoresis. Proteins that varied significantly in concentration were selected and identified using mass spectrometry. Expression of translationally controlled tumor protein (TCTP) mRNA and protein in LoVo-PRL-3 and LoVo-control cells was detected by real-time PCR and Western blotting. Small interfering RNA (siRNA) targeting TCTP was used for silencing TCTP expression in LoVo-PRL-3 cells. Functional significance of TCTP in PRL-3-promoted colon cancer cell proliferation, migration and invasion was investigated by Cell Counting Kit-8 assay and transwell chamber. Results Seventeen proteins displaying significant and reproducible differences between LoVo-PRL-3 and LoVo-control cells were identified. Ten proteins were upregulated and seven were downregulated in LoVo-PRL-3 cells when compared with LoVo-control cells. Eight identified proteins are associated with distinct steps of tumor metastasis: ubiquitin-like protein ISG15, interleukin-18, TCTP, serpin B5, annexin A3, macrophage-capping protein, ATP-dependent RNA helicase DDX3X, and cathepsin D. Real-time PCR and Western blotting results showed that both TCTP mRNA and protein were significantly increased in LoVo-PRL-3 cells compared to LoVo-control cells. Transfection with TCTP siRNA significantly reduced the expression of both mRNA and protein levels of TCTP in LoVo-PRL-3 cells. Knockdown of TCTP by siRNA inhibited PRL-3-promoted proliferation, migration and invasion of LoVo-PRL-3 cells. Conclusion Our results imply that TCTP might be a mediator of PRL-3-prom展开更多
目的:研究miR495、miR551a干扰质粒对SGC7901胃癌细胞中促肝细胞再生磷酸酶-3(phosphatase of regenerating liver-3,PRL-3)表达的影响,探讨基因干扰在胃癌治疗中的价值.方法:分别体外培养稳定转染后的SGC7901细胞系及未经处理的SGC790...目的:研究miR495、miR551a干扰质粒对SGC7901胃癌细胞中促肝细胞再生磷酸酶-3(phosphatase of regenerating liver-3,PRL-3)表达的影响,探讨基因干扰在胃癌治疗中的价值.方法:分别体外培养稳定转染后的SGC7901细胞系及未经处理的SGC7901细胞系,取对数生长期瘤细胞,0.5mL(1×107/mL)细胞悬液接种于Balb/ca(nu/nu)裸鼠腹腔内,在SPF条件下饲养1mo后处死,观察裸鼠成瘤率、瘤体生长情况及腹膜转移等情况,并行组织病理学检查.取各组部分移植瘤行荧光定量PCR检测,对比各组miR495、miR551a及PRL-3mRNA的相对表达水平.结果:各组裸鼠成瘤率均100%,其中两实验组裸鼠一般情况及生存期均好于对照组.取各组移植瘤行荧光定量PCR检测显示,两实验组裸鼠miRNA表达量显著高于对照组,PRL-3mRNA表达量低于对照组.转染质粒组胃癌迁移能力明显减弱.结论:转染靶向干扰PRL-3表达的miR495、mi551a真核质粒可以明显抑制胃癌细胞体内转移侵袭能力.展开更多
文摘Protein tyrosine phosphorylation is a major posttranslational modification used by cells to regulate signal transduction and essentially participate in every aspect of cellular physiologic and pathogenic processes. The protein tyrosine phosphatase (PTP) super family of enzymes coordinately function with protein tyrosine kinases in signaling pathways that underlie a broad spectrum of fundamental physiological processes. Abnormal regulation of tyrosine phosphorylation or deregulation of phosphorylation is known to result in neoplastic or non-neoplastic diseases. Having evolved into separate families that are structurally and mechanistically distinct, PTPs have been implicated in a variety of diseases and efforts have been made to seek therapeutic clues from them. The phosphatases of regenerating liver (PRL) PRL-1, PRL-2, PRL-3 (also known as PTP4A1, PTP4A2, and PTP4A3, respectively) constitute a subfamily of the protein tyrosine phosphatases that have been suggested to play a key role in oncogenic and metastatic phenotypes.5 Here we review what is known about this novel class of small, prenylated phosphatases and its value in diagnosis and therapy of solid tumors.
文摘目的:研究肝再生磷酸酶-3(phosphatase of regenerating liver,PRL-3)与鼻腔鼻窦鳞状细胞癌分化程度的关系,及其对鼻腔鼻窦鳞状细胞癌发病机制中的分子生物学作用,了解其相关性,从而使患者早期确诊,并对其预后的判断给予指导。方法:采用免疫组化法对30例不同程度的鼻腔鼻窦鳞癌组织行PRL-3检测,并用20例鼻腔正常黏膜组织做为对照。结果:PRL-3在各级鼻腔鼻窦鳞癌组织中均有表达,与正常鼻黏膜比较有显著差异(P<0.05),随着鳞癌分级的升高其表达具有增强的趋势。结论:PRL-3在鼻腔鼻窦鳞状细胞癌中比在鼻息肉组织中表达显著增高,表明其可能与鼻腔鼻窦鳞癌的发生有关,可能是鳞癌发生的早期事件。
文摘Background Considerable evidence suggests that phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in cancer metastasis; however, the molecular mechanisms remain largely unknown. The aim of this study was to identify proteins associated with PRL-3-promoted colon cancer metastasis, by comparative proteomic analysis. Methods Proteomes of human colon cancer LoVo cells transfected with PRL-3 gene (LoVo-PRL-3) or empty vector PAcGFP-C3 (LoVo-control) were compared using 2D gel electrophoresis. Proteins that varied significantly in concentration were selected and identified using mass spectrometry. Expression of translationally controlled tumor protein (TCTP) mRNA and protein in LoVo-PRL-3 and LoVo-control cells was detected by real-time PCR and Western blotting. Small interfering RNA (siRNA) targeting TCTP was used for silencing TCTP expression in LoVo-PRL-3 cells. Functional significance of TCTP in PRL-3-promoted colon cancer cell proliferation, migration and invasion was investigated by Cell Counting Kit-8 assay and transwell chamber. Results Seventeen proteins displaying significant and reproducible differences between LoVo-PRL-3 and LoVo-control cells were identified. Ten proteins were upregulated and seven were downregulated in LoVo-PRL-3 cells when compared with LoVo-control cells. Eight identified proteins are associated with distinct steps of tumor metastasis: ubiquitin-like protein ISG15, interleukin-18, TCTP, serpin B5, annexin A3, macrophage-capping protein, ATP-dependent RNA helicase DDX3X, and cathepsin D. Real-time PCR and Western blotting results showed that both TCTP mRNA and protein were significantly increased in LoVo-PRL-3 cells compared to LoVo-control cells. Transfection with TCTP siRNA significantly reduced the expression of both mRNA and protein levels of TCTP in LoVo-PRL-3 cells. Knockdown of TCTP by siRNA inhibited PRL-3-promoted proliferation, migration and invasion of LoVo-PRL-3 cells. Conclusion Our results imply that TCTP might be a mediator of PRL-3-prom
文摘目的:研究miR495、miR551a干扰质粒对SGC7901胃癌细胞中促肝细胞再生磷酸酶-3(phosphatase of regenerating liver-3,PRL-3)表达的影响,探讨基因干扰在胃癌治疗中的价值.方法:分别体外培养稳定转染后的SGC7901细胞系及未经处理的SGC7901细胞系,取对数生长期瘤细胞,0.5mL(1×107/mL)细胞悬液接种于Balb/ca(nu/nu)裸鼠腹腔内,在SPF条件下饲养1mo后处死,观察裸鼠成瘤率、瘤体生长情况及腹膜转移等情况,并行组织病理学检查.取各组部分移植瘤行荧光定量PCR检测,对比各组miR495、miR551a及PRL-3mRNA的相对表达水平.结果:各组裸鼠成瘤率均100%,其中两实验组裸鼠一般情况及生存期均好于对照组.取各组移植瘤行荧光定量PCR检测显示,两实验组裸鼠miRNA表达量显著高于对照组,PRL-3mRNA表达量低于对照组.转染质粒组胃癌迁移能力明显减弱.结论:转染靶向干扰PRL-3表达的miR495、mi551a真核质粒可以明显抑制胃癌细胞体内转移侵袭能力.