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Du Y.,Shanghai JiaoTong University | Bi W.,Weifang Hospital of Chinese Traditional Medicine | Zhang F.,Shanghai JiaoTong University | Wu W.,Shanghai JiaoTong University | And 2 more authors.
Biotechnology and Applied Biochemistry | Year: 2015

Urinary bladder cancer is a worldwide concern because of its level of incidence and recurrence. To search an effective therapeutic strategy for urinary bladder cancer, it is important to identify proteins involved in tumorigenesis that could serve as potential targets for diagnosis and treatment. G-protein-coupled receptors (GPRs) constitute a large protein family of receptors that sense molecules outside the cell and activate signal transduction pathways and cellular responses inside the cell. GPR137 is a newly discovered human gene encoding orphan GPRs. In this study, we aimed to investigate the physiological role of GPR137 in urinary bladder cancer. The effect of GPR137 on cell growth was examined via an RNA interference (RNAi) lentivirus system in two human urinary bladder cancer cell lines BT5637 and T24. Lentivirus-mediated RNAi could specifically suppressed GPR137 expression in vitro, resulting in alleviated cell viability and impaired colony formation, as well as blocks G0/G1 and S phases of the cell cycle. These results suggested GPR137 as an essential player in urinary bladder cancer cell growth, and it may serve as a potential target for gene therapy in the treatment of urinary bladder cancer. © 2014 International Union of Biochemistry and Molecular Biology, Inc.


Du Y.,Shanghai JiaoTong University | Wang Y.,Weifang Hospital of Chinese Traditional Medicine | Zhang F.,Shanghai JiaoTong University | Wu W.,Shanghai JiaoTong University | And 4 more authors.
Tumor Biology | Year: 2015

Bladder cancer (BC) is the most popular malignant urinary cancer, with the highest incidence and mortality of all genitourinary system tumors worldwide. To date, the molecular regulation of the metastasis of BC remains ill defined. Here, we examined the levels of matrix metallopeptidase 9 (MMP9) and nuclear β-catenin in the BC specimen. We used lithium chloride (LiCl) to inhibit cytosol β-catenin phosphorylation and degradation to increase nuclear β-catenin levels in BC cells. We used IWP-2 to enhance cytosol β-catenin phosphorylation and degradation to decrease nuclear β-catenin levels in BC cells. We examined MMP9 levels in these experimental settings by quantitative reverse transcription-PCR (RT-qPCR), Western blot, and ELISA. The cell invasiveness was evaluated by Transwell cell assay. We found significantly higher levels of MMP9 and nuclear β-catenin in human BC specimen with metastasis, compared to those without metastasis. Moreover, a strong correlation was detected between MMP9 and nuclear β-catenin. LiCl significantly increased nuclear β-catenin, resulting in MMP9 activation in BC cells. IWP-2 significantly decreased nuclear β-catenin, resulting in MMP9 inhibition in BC cells. MMP9 regulated cell invasiveness. Together, these data suggest that the WNT signaling pathway regulates metastasis of BC through activation of MMP9. Therapies targeting the WNT signaling pathway may be a promising treatment for BC. © 2015, International Society of Oncology and BioMarkers (ISOBM).


PubMed | Weifang Hospital of Chinese Traditional Medicine and Shanghai JiaoTong University
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2015

Bladder cancer (BC) is the most popular malignant urinary cancer, with the highest incidence and mortality of all genitourinary system tumors worldwide. To date, the molecular regulation of the metastasis of BC remains ill defined. Here, we examined the levels of matrix metallopeptidase 9 (MMP9) and nuclear -catenin in the BC specimen. We used lithium chloride (LiCl) to inhibit cytosol -catenin phosphorylation and degradation to increase nuclear -catenin levels in BC cells. We used IWP-2 to enhance cytosol -catenin phosphorylation and degradation to decrease nuclear -catenin levels in BC cells. We examined MMP9 levels in these experimental settings by quantitative reverse transcription-PCR (RT-qPCR), Western blot, and ELISA. The cell invasiveness was evaluated by Transwell cell assay. We found significantly higher levels of MMP9 and nuclear -catenin in human BC specimen with metastasis, compared to those without metastasis. Moreover, a strong correlation was detected between MMP9 and nuclear -catenin. LiCl significantly increased nuclear -catenin, resulting in MMP9 activation in BC cells. IWP-2 significantly decreased nuclear -catenin, resulting in MMP9 inhibition in BC cells. MMP9 regulated cell invasiveness. Together, these data suggest that the WNT signaling pathway regulates metastasis of BC through activation of MMP9. Therapies targeting the WNT signaling pathway may be a promising treatment for BC.


PubMed | Weifang Hospital of Chinese Traditional Medicine and Shanghai JiaoTong University
Type: Journal Article | Journal: Biotechnology and applied biochemistry | Year: 2016

Urinary bladder cancer is a worldwide concern because of its level of incidence and recurrence. To search an effective therapeutic strategy for urinary bladder cancer, it is important to identify proteins involved in tumorigenesis that could serve as potential targets for diagnosis and treatment. G-protein-coupled receptors (GPRs) constitute a large protein family of receptors that sense molecules outside the cell and activate signal transduction pathways and cellular responses inside the cell. GPR137 is a newly discovered human gene encoding orphan GPRs. In this study, we aimed to investigate the physiological role of GPR137 in urinary bladder cancer. The effect of GPR137 on cell growth was examined via an RNA interference (RNAi) lentivirus system in two human urinary bladder cancer cell lines BT5637 and T24. Lentivirus-mediated RNAi could specifically suppressed GPR137 expression in vitro, resulting in alleviated cell viability and impaired colony formation, as well as blocks G0/G1 and S phases of the cell cycle. These results suggested GPR137 as an essential player in urinary bladder cancer cell growth, and it may serve as a potential target for gene therapy in the treatment of urinary bladder cancer.


Wang Y.C.,Weifang Hospital of Chinese Traditional Medicine
Zhonghua nan ke xue = National journal of andrology | Year: 2012

To study the gene expressions in the stromal cells of the human prostate peripheral zone (PZ) in men of different ages. We primarily cultured stromal cells from the normal prostate PZ of men aged 23 -32 (young group) and 56 -75 years (old group), profiled the gene signature of the PZ cells by cDNA microarray, and defined the differential gene expression patterns by hierarchical cluster analysis. Among the differential genes, we selected and confirmed up-regulated genes by quantitative real time PCR (Q-PCR), and identified their protein coding by Western blotting. There were significant differences in the gene expressions of the PZ cells between the old and young groups. Based on the fold change ratio of > or = 2 or < or = 0.5, 509 up-regulated and 188 down-regulated genes were selected in the PZ cells. A subset of significantly differential genes influencing the growth of adjacent epithelial cells were identified, including HGF, IGF2, IGFBP5 and MMP1 in the old males. Stromal cells in the prostate PZ were more active in older males in promoting the malignant progression of adjacent prostate epithelial cells, which might be due to the increased expression of extracellular paracrining mediators.


Liang Y.,Weifang Hospital of Chinese Traditional Medicine | Zhuang J.,Weifang Hospital of Chinese Traditional Medicine | Sun C.-G.,Weifang Hospital of Chinese Traditional Medicine
Chinese Journal of Cancer Prevention and Treatment | Year: 2013

OBJECTIVE: To sum up the characteristic of Aldehyde dehydrogenase 1 and the association study that ALDH1 as the stem cell marker of breast cancer in recent years. METHODS: The following keywords: breast tumor, ALDH1, stem cell, immunohistochemistry proteomics were used and the database of PubMed, Elsevier Sciencedirect and CNKI Academic Journal were searched; The limited time was 2002.01-2012.11. Totally 256 related literatures were srarched. Standards of getting out: non-breast cancer, non-ALDH1. Enrolled criteria: 1)The correlation study of breast cancer and ALDH1. 2)The method to study breast cancer stem cells was immunohistochemical method and proteomics. Eighteen literatures were included in this review. RESULTS: Many studies which invovled immunohistochemistry, proteomics, clinical trials and so on shows that ALDH1+ cells met the standard definition of stem cells (self proliferation and multi-differentiation). ALDH1 is confirmed as an effective mark of stem cell in many tissues and can be detected by several methods, which make it a powerful tool in the identification and isolation of stem cells. ALDH1 can make great significance in the field of stem cell research. As one of the marks of breast cancer stem cell, ALDH1 is associated with many clinic-pathological factors, can reflect the degree of malignancy and prognosis of the disease to a certain extent and it was the root of tumorigenesis, progression, drug resistance, and poor prognosis in breast cancer. CONCLUSIONS: With respect to biological characteristics of ALDH1, further investigation on the characteristics as the stem cell marker of breast cancer may help us provide theoretical basis for individualized treatment of breast cancer.

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