c-myc Promoter-binding Protein 1 (MBP-1) Regulates Prostate Cancer Cell Growth by Inhibiting MAPK Pathway

Ghosh, Asish K.; Steele, Robert; Ray, Ratna B.

doi:10.1074/jbc.m413313200

Cited by 46 publications

(57 citation statements)

References 37 publications

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“…Preoperative prostate-specific antigen (pre-PSA) level ranged from 0.3 to 97.5 ng/mL (mean, 10.36 ng/mL), with 30% of patients having a pre-PSA level greater than 10.36 ng/mL. Lower Gleason score (GS) (3)(4)(5)(6) was present in 33% patients, whereas 67% had a higher GS (7)(8)(9)(10). Biochemical recurrence occurred in 15.5% of patients, whereas 5.6% had lymph node (LN) metastases.…”

Section: Clinical and Pathologic Characteristicsmentioning

confidence: 99%

“…This could explain why PCa can respond to initial androgen withdrawal, but many patients with PCa end up with recurrence and androgen independence, leading to accelerated disease progression and death [2,3]. A number of regulatory pathways such as androgen receptor (AR) signaling pathway [4,5], mitogen-activated protein kinase signaling pathway [6], and Akt/PKB (protein kinase B) signaling pathway [7,8] may play critical roles in prosurvival/proliferation in PCa.…”

Section: Introductionmentioning

confidence: 99%

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Forkhead protein FKHR and its phosphorylated form p-FKHR in human prostate cancer

Erdamar

Dai

et al. 2007

Human Pathology

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SummaryIn vitro studies suggest that the proapoptotic function of forkhead protein FKHR is probably inactivated by means of phosphorylation through the protein kinase B pathway. However, the clinical significance of FKHR in prostate cancer remains unclear. Six hundred forty radical prostatectomies were used for building tissue microarrays. Slides were stained with antibodies against FKHR and phosphorylated FKHR (p-FKHR). Correlations with clinicopathologic parameters were analyzed by Spearman rank test. Cox regression test and Kaplan-Meier test were used to determine the probability of disease recurrence, which is defined as a serum prostate-specific antigen (PSA) level greater than 0.4 ng/mL after radical prostatectomy. Nuclear FKHR level was higher in normal prostate than in benign prostatic hyperplasia and prostate cancer (P = .0000). Nuclear expression of FKHR was correlated with preoperative PSA level (ρ = 0.108, P = .029), extracapsular extension (ρ = 0.137, P = .005), and seminal vesicle invasion (ρ = 0.101, P = .039). FKHR expression was not a significant indicator of biochemical failure by either univariate or multivariate analysis. Nuclear p-FKHR expression correlated with patients' age (ρ = 0.179, P = .0003), Gleason score (ρ = 0.130, P = .0083), extracapsular extension (ρ = 0.227, P = .0000), clinical stage (Union Internationale Contre le Cancer system) (ρ = 0.166, P = .0007), and lymph node status (ρ = 0.101, P = .0401). Cytoplasmic p-FKHR correlated with patients' age (ρ = 0.146, P = .0030) and clinical stage (ρ = 0.117, P = .0180). Cytoplasmic p-FKHR was a significant indicator of biochemical recurrence (P = .0164; hazard ratio, 1.114-2.929). Nuclear p-FKHR strongly correlated with phosphorylated protein kinase B (ρ = 0.368, P = .0000), androgen receptor (ρ = 0.385, P = .0000), and Skp-2 (ρ = 0.170, P = .0036). Our data suggest that the proapoptotic role of FKHR is probably regulated by several signaling pathways in prostate cancer.

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Section: Clinical and Pathologic Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Forkhead protein FKHR and its phosphorylated form p-FKHR in human prostate cancer

Erdamar

Dai

et al. 2007

Human Pathology

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“…In addition to c-Myc, cyclin D1 expression is also suppressed by MBP-1 (Ghosh et al, 2005a). Therefore, effects of MBP-1 on mRNA expressions of COX-2, c-Myc, and cyclin D1 were also evaluated in SC-M1/HA-MBP-1 #6 cells by real-time PCR.…”

Section: Mbp-1 Binds On Human Cox-2 Promoter and Downregulates Cox-2 mentioning

confidence: 99%

“…The 37-kDa MBP-1 is produced by alternative translation initiation from ␣-enolase gene but without enzyme activity of enolase (Feo et al, 2000;Subramanian and Miller, 2000). So far, several MBP-1-associating proteins were identified, including histone deacetylase HDAC1 (Ghosh et al, 1999), MIP2A/sedlin (Ghosh et al, 2001), MEK5␣ (Ghosh et al, 2005a), NS1-BP (Perconti et al, 2007), and Notch1 receptor intracellular domain (Hsu et al, 2008). The downstream target genes of MBP-1 remain unclear exclusive of c-myc.…”

Section: Introductionmentioning

confidence: 99%

“…Mounting evidence indicates that both MBP-1 and ␣-enolase are involved in tumorigenesis of breast carcinoma (Ray et al, 1995), nonsmall cell lung cancer (Chang et al, 2003;Ghosh et al, 2006b), hepatitis C virus-related hepatocellular carcinoma (Takashima et al, 2005), prostate tumor (Ghosh et al, 2005a;Ghosh et al, 2005b;Ghosh et al, 2006a), and neuroblastoma (Ejeskar et al, 2005). It was also suggested that MBP-1 expression reduces the invasive ability of breast cancer (Ray et al, 1995), and ␣-enolase may participate in control of EMT (Demir et al, 2005) and metastasis (Chang et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

Hsu

Hsieh

et al. 2009

MBoC

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INTRODUCTIONGastric cancer is one of the most frequent neoplasms and leading causes of cancer-related mortality worldwide (Terry et al., 2002;Executive Yuan, 2006). At present, curative surgery of its primary tumor and control of lymph node metastasis are still the mainstay of treatment for gastric cancer without distant metastasis . However, gastric cancer with distant metastasis remains incurable now. More than 95% of malignancies of the stomach are adenocarcinomas (Smith et al., 2006). The risk factors of human gastric cancer include diet, Helicobacter pylori infection, and accumulation of specific genetic alterations (Gonzalez et al., 2002;Ushijima and Sasako, 2004;Zheng et al., 2004). To date, the regulatory mechanism of aggressiveness in gastric cancer has not yet been clearly characterized. Therefore, it is essential to gain further insights into the physiology of gastric cancer and its accumulated genetic alterations.The inducible cyclooxygenase, COX-2, catalyzes the ratelimiting step in conversion of arachidonate into prostaglandin E 2 (PGE 2 ). It was shown that COX-2 expression is upregulated in gastric cancer (Ristimäki et al., 1997;Uefuji et al., 1998;Yamamoto et al., 1999;Lim et al., 2000). COX-2 expression is also correlated with depth of invasion, lymphatic vessel invasion, lymph node metastasis, and poor prognosis of human gastric carcinoma (Murata et al., 1999;Ohno et al., 2001;Shi et al., 2003;Chen et al., 2006). Epithelial-mesenchymal transition (EMT) plays a key role in development and tumorigenesis (for a review, see Thiery and Sleeman, 2006). In gastric cancer cells with fibroblastoid morphological changes, EMT signaling was suggested to promote motility and invasiveness through decreasing cell-cell adhesion (Katoh, 2005). Recently, COX-2 expression was found to enhance EMT stimulated by TGF-␤ through a PGE 2 -dependent manner in breast cancer (Neil et al., 2008). In this scenario, the induction of COX-2 expression in gastric cancer could further induce EMT to promote metastasis.The c-Myc promoter binding protein 1 (MBP-1), a negative regulator of c-myc expression, is ubiquitously expressed in normal human tissues (Ray et al., 1994 groove of the major c-Myc promoter, the P2 promoter (Chaudhary and Miller, 1995). The 37-kDa MBP-1 is produced by alternative translation initiation from ␣-enolase gene but without enzyme activity of enolase (Feo et al., 2000;Subramanian and Miller, 2000). So far, several MBP-1-associating proteins were identified, including histone deacetylase HDAC1 (Ghosh et al., 1999), MIP2A/sedlin (Ghosh et al., 2001), MEK5␣ (Ghosh et al., 2005a), NS1-BP (Perconti et al., 2007), and Notch1 receptor intracellular domain (Hsu et al., 2008). The downstream target genes of MBP-1 remain unclear exclusive of c-myc. It was reported that MBP-1 could regulate target genes at least through p53-p21 pathway (Ghosh et al., 2008). Mounting evidence indicates that both MBP-1 and ␣-enolase are involved in tumorigenesis of breast carcinoma (Ray et al., 1995), nonsmall cell lung cancer (Chan...

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RN181 suppresses hepatocellular carcinoma growth by inhibition of the ERK/MAPK pathway

Wang

Huang

et al. 2011

Hepatology

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The activation of oncogenes and the inactivation of tumor suppressor genes by mutations or chronic hepatitis virus infections play key roles in the pathogenesis of hepatocellular carcinoma (HCC). Here we report that RN181, a really interesting new gene finger domain-containing protein, was down-regulated in highly malignant cell lines and in tumor cells of 139 HCC clinical samples in comparison with adjacent normal liver tissues. The expression of RN181 was strongly associated with the pathological grade of HCC. Alterations of the expression of RN181 by retrovirus-transduced up-regulation and short hairpin RNA-mediated down-regulation demonstrated the function of RN181 as a tumor suppressor because it decreased the proliferation and colony formation of HCC cells in vitro and inhibited tumor growth in vivo by suppressing cell proliferation and enhancing cell apoptosis in xenografted tumors. Proteomic analyses showed that RN181 regulates the expression of many proteins that are important in many cellular processes. Statistical analyses identified 33 proteins with consistent changes (!2-fold) in RN181-transformed cells. Ten of these proteins were up-regulated by RN181, and 23 were down-regulated. Representative proteins were validated by western blotting. Interaction network investigations revealed that 20 RN181-regulated proteins could integrate several key biological processes such as survival, metabolism, and mitogen-activated protein kinase (MAPK) pathways. Remarkably, 11 of the 33 proteins are associated with MAPK signaling in one or more ways. RN181 suppressed the tyrosine phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in cell lines and in tumor cells of xenografts and HCC clinical samples, and removing the suppression increased tumor growth. Conclusion: We have shown that RN181 suppresses the tumorigenesis of HCC through the inhibition of ERK/MAPK signaling in the liver. Our results provide new insights into the pathogenesis of HCC and may help with the development of novel therapeutic strategies. (HEPATOLOGY

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c-myc Promoter-binding Protein 1 (MBP-1) Regulates Prostate Cancer Cell Growth by Inhibiting MAPK Pathway

Cited by 46 publications

References 37 publications

Forkhead protein FKHR and its phosphorylated form p-FKHR in human prostate cancer

Forkhead protein FKHR and its phosphorylated form p-FKHR in human prostate cancer

MBP-1 Suppresses Growth and Metastasis of Gastric Cancer Cells through COX-2

RN181 suppresses hepatocellular carcinoma growth by inhibition of the ERK/MAPK pathway

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