Clinicopathological significance of B-cell-specific Moloney murine leukemia virus insertion site 1 expression in gastric carcinoma and its precancerous lesion

Zhao, Jing; Luο, Xingguang; Chen, Da

doi:10.3748/wjg.15.2145

Cited by 10 publications

(13 citation statements)

References 13 publications

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“…Consistent with its tumor suppressor role, we also found that Mel-18 negatively regulated AKT expression, and induced p16 expression and senescence in gastric cancer cell lines. In a recent study, BMI1 overexpression was closely related with the Lauren's and Borrmann's classification and clinical stage in gastric tumors [29]. However, in our study we did not find correlation between BMI1 expression and tumor size, T classification or differentiation in gastric tumors, which was not consistent with the in vitro study that BMI1 regulates proliferation.…”

Section: Discussioncontrasting

confidence: 99%

BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

Zhang

Sheng

et al. 2010

Mol Cancer

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BackgroundThe BMI1 oncogene is overexpressed in several human malignancies including gastric cancer. In addition to BMI1, mammalian cells also express Mel-18, which is closely related to BMI1. We have reported that Mel-18 functions as a potential tumor suppressor by repressing the expression of BMI1 and consequent downregulation of activated AKT in breast cancer cells. However, the mechanisms of BMI1 overexpression and the role of Mel-18 in other cancers are still not clear. The purpose of this study is to investigate the role of BMI1 and Mel-18 in gastric cancer.ResultsBMI1 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of BMI1 correlated with advanced clinical stage and lymph node metastasis; while the expression of Mel-18 negatively correlated with BMI1. BMI1 but not Mel-18 was found to be an independent prognostic factor. Downregulation of BMI1 by Mel-18 overexpression or knockdown of BMI1 expression in gastric cancer cell lines led to upregulation of p16 (p16INK4a or CDKN2A) in p16 positive cell lines and reduction of phospho-AKT in both p16-positive and p16-negative cell lines. Downregulation of BMI1 was also accompanied by decreased transformed phenotype and migration in both p16- positive and p16-negative gastric cancer cell lines.ConclusionsIn the context of gastric cancer, BMI1 acts as an oncogene and Mel-18 functions as a tumor suppressor via downregulation of BMI1. Mel-18 and BMI1 may regulate tumorigenesis, cell migration and cancer metastasis via both p16- and AKT-dependent growth regulatory pathways.

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Section: Discussioncontrasting

confidence: 99%

BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

Zhang

Sheng

et al. 2010

Mol Cancer

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“…High BMI-1 expression was associated with welldifferentiated and intestinal-type histology, which are favorable prognostic factors in gastric cancers [23,26,27]. In the aspect of other clinicopathologic variables predicting prognosis such as age, lymphovascular invasion, perineural invasion, depth of invasion, lymph node metastasis, and anatomic TNM stage group [26,27], there was no important correlation according to the expression level of the 4 proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Such conflicting findings predict both oncogenic and tumor suppressive activities for PcG proteins. Some studies suggested that aberrant BMI-1 or EZH2 expression might serve as prognostic factors [12,13,[20][21][22][23][24][25]. Overexpressions of BMI-1 or EZH2 are associated with gastric cancer cell proliferation, invasion, and metastasis [12,13,20,22,24].…”

Section: Introductionmentioning

confidence: 98%

Immunohistochemical analysis of polycomb group protein expression in advanced gastric cancer

et al. 2012

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“…BMI1 is active in stem cells and in several tumors, including gastric and prostatic adenocarcinomas (323,324).…”

Section: Ebvmentioning

confidence: 99%

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

Sinkovics

2011

Int J Oncol

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Abstract. In some inflammasomes tumor cells are generated. The internal environment of the inflammasome is conducive to the induction of malignant transformation. Epigenetic changes initiate this process. The subverted stromal connective tissue cells act to promote and sustain the process of malignant trans formation. In its early stages, the premalignant cells depend on paracrine circuitries for the reception of growth factors. The ligands are derived from the connective tissue, and the receptors are expressed on the recipient premalignant cells. The initial events are not a direct attack on the protooncogenes, and thus it may be entirely reversible. Epigenetic processes of hypermethylation of the genes at the promoters of tumor suppressor genes (to silence them), and deacetylation of the histones aimed at the promoters of protooncogenes (to activate them) are ongoing. A large number of short RNA sequences (interfering, micro, short hairpin, noncoding RNAs) silence tumor suppressor genes, by neutralizing their mRNAs. In a serial sequence oncogenes undergo amplifications, pointmutations, translocations and fusions. In its earliest stage, the process is reversible by demethylation of the silenced suppressor gene promoters (to reactivate them), or reacetylation of the histones of the oncogene promoters, thus deactivating them. The external administration of histone deacetylase inhibitors usually leads to the restoration of histone acetylation. In time, the uncorrected processes solidify into constitutive and irreversible gene mutations. Some of the pathogens inducing inflammations with consquential malignant transformation contain oncogenic gene sequences (papilloma viruses, EpsteinBarr virus, Kaposi's sarcomaassociated herpesvirus, hepatitis B and C viruses, Merkel cell polyoma virus, Helicobacter pylori, enterotoxigenic Bacteroides fragilis). These induced malignancies may be multifocal. Other pathogens are devoid of any known oncogenic genomic sequences (mycoplasma vavcarcinogenesis, chlamydia MALTlymphoma genesis). In these cases the host's inflammatory reactions induce the malignant transformation in serial sequences of gene alterations initiated by hypoxia and reactive oxygen and nitrogen species generation. Carcinogenic intrinsic inflammatory processes endogenously initiated without a pathogen are recognized. Chronic inflammatory processes signal the RNA/DNA complex. In response, the DNA may revert into its ancient primordial 'immortal' format, which the clinics recognize as 'oncogenesis'. The DNA remains the ultimate master of bioengineering in order to sustain life. A discussion on the most versatile and resistant primordial RNA/ DNA complex and the pre, proto, and unicellular world in which they coexisted is included. Contents1. Pathogens without oncogenic genomic sequences activating cellular oncogenes 2. The inflammasome 3. Tumor cell colonies generated in the inflammasomes 4. Pathogens with potentially oncogenic genomic sequences 5. Mechanisms of inflammatory carcinogenesis Pathogens without oncogenic...

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Clinicopathological significance of B-cell-specific Moloney murine leukemia virus insertion site 1 expression in gastric carcinoma and its precancerous lesion

Cited by 10 publications

References 13 publications

BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

BMI1 and Mel-18 oppositely regulate carcinogenesis and progression of gastric cancer

Immunohistochemical analysis of polycomb group protein expression in advanced gastric cancer

Molecular biology of oncogenic inflammatory processes. I. Non-oncogenic and oncogenic pathogens, intrinsic inflammatory reactions without pathogens, and microRNA/DNA interactions (Review)

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