Transfer of bcl-xs plasmid is effective in preventing and inhibiting rat hepatocellular carcinoma induced by N-nitrosomorpholine

Baba, Miyako; Tatsuta, Masaharu

doi:10.1038/sj.gt.3301504

Cited by 12 publications

(5 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When the tumors had grown to ϳ2.5 mm in diameter, mice were randomly divided into three groups of five tumor-bearing mice. In vivo electroporation was performed to deliver naked DNA into pre-established tumors (18,19). Briefly, 20 g of plasmid DNA in 30 l of saline was injected into the tumors of tumor-bearing mice.…”

Section: Molecular Cloning Of Full-length Human Cyclin L2 and Its Moumentioning

confidence: 99%

Cyclin L2, a Novel RNA Polymerase II-associated Cyclin, Is Involved in Pre-mRNA Splicing and Induces Apoptosis of Human Hepatocellular Carcinoma Cells

Yang¹,

Li²,

Wang

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

We report the cloning and functional characterization of human cyclin L2, a novel member of the cyclin family. Human cyclin L2 shares significant homology to cyclin L1, K, T1, T2, and C, which are involved in transcriptional regulation via phosphorylation of the C-terminal domain of RNA polymerase II. The cyclin L2 protein contains an N-terminal ''cyclin box'' and C-terminal dipeptide repeats of alternating arginines and serines, a hallmark of the SR family of splicing factors. A new isoform and the mouse homologue of human cyclin L2 have also been cloned in this study. Human cyclin L2 is expressed ubiquitously in normal human tissues and tumor cells. We show here that cyclin L2 co-localizes with splicing factors SC-35 and 9G8 within nuclear speckles and that it associates with hyperphosphorylated, but not hypophosphorylated, RNA polymerase II and CDK p110 PITSLRE kinase via its N-terminal cyclin domains. It can also associate with the SC-35 and 9G8 through its RS repeat region. Recombinant cyclin L2 protein can stimulate in vitro mRNA splicing. Overexpression of human cyclin L2 suppresses the growth of human hepatocellular carcinoma SMMC 7721 cells both in vitro and in vivo, inducing cellular apoptosis. This process involves up-regulation of p53 and Bax and decreased expression of Bcl-2. The data suggest that cyclin L2 represents a new member of the cyclin family, which might regulate the transcription and RNA processing of certain apoptosis-related factors, resulting in tumor cell growth inhibition and apoptosis.Cyclins are key regulatory proteins that complex with and activate cyclin-dependent kinase (CDK) 1 subunits (1-4), playing pivotal roles in the regulation of cell cycle progression (5).Cyclins may be currently classified into two major groups, seemingly reflecting their functions. The cell cycle regulator cyclins, composed primarily of cyclin A, B, D1, D2, D3, E, and F, function with their CDK partners including CDK1, -2, -3, and -4 to regulate promotion of the cell cycle. The transcription regulator cyclins, which include cyclin C, H, K, L1, T1, and T2, work together with CDK7, -8, and -9 and tend to play roles in transcriptional regulation (6). The proposed functions of cyclin G 1 and G 2 are seemingly distinct from either cell cycle or transcriptional regulation (7). Other cyclins have also been identified, but their roles in cell cycle control and RNA transcription, if any, are unclear and remain to be studied.Transcription regulator cyclin/CDK pairs are associated with the initiation, elongation, and processing of RNA transcripts. During this process cyclins interact with the large subunit of RNA polymerase II, phosphorylating the C-terminal domain (CTD) via their partner CDKs. It is widely accepted that transcription and RNA processing are closely related. Capping enzymes, polyadenylation factors, and splicing factors assemble at the CTD of RNA polymerase II. Hyperphosphorylated RNA polymerase II (RNAPIIo) stimulates RNA splicing, and the CTD has been observed to target some splicing factors to R...

show abstract

Section: Molecular Cloning Of Full-length Human Cyclin L2 and Its Moumentioning

confidence: 99%

Cyclin L2, a Novel RNA Polymerase II-associated Cyclin, Is Involved in Pre-mRNA Splicing and Induces Apoptosis of Human Hepatocellular Carcinoma Cells

Yang¹,

Li²,

Wang

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…21 Furthermore, infection with an adenoviral vector containing Bcl-x S cDNA specifically induces apoptosis in several types of cancer cells, [22][23][24][25] and transfer of Bcl-x S plasmid is effective in preventing and inhibiting rat hepatocellular carcinoma induced by N-nitrosomorpholine. 26 Unraveling the mechanism of Bcl-x S -induced apoptosis could therefore have important clinical implications.…”

mentioning

confidence: 99%

Bak but not Bax is essential for Bcl-xS-induced apoptosis

et al. 2005

View full text Add to dashboard Cite

Bcl-x S , a proapoptotic member of the Bcl-2 protein family, is localized in the mitochondria and induces apoptosis in a caspase-and BH3-dependent manner by a mechanism involving cytochrome c release. The way in which Bcl-x S induces caspase activation and cytochrome c release, as well as the relationship between Bcl-x S and other proapoptotic members of the Bcl-2 family, is not known. Here we used embryonic fibroblasts derived from mice deficient in the multidomain proapoptotic members of the Bcl-2 family (Bax and Bak) and the apoptotic components of the apoptosome (Apaf-1 and caspase-9) to unravel the cascade of events by which Bcl-x S promotes apoptosis. Our results show that Bak but not Bax is essential for Bcl-x S -induced apoptosis. Bcl-x S induced activation of Bak, which in turn promoted apoptosis by apoptosome-dependent and -independent pathways. These findings provide the first evidence that a proapoptotic Bcl-2 family protein induces apoptosis exclusively via Bak.

show abstract

“…The viral protein HCV NS3 stimulated proliferation in NIH 3T3 cells, an effect associated with p53-dependent repression of p21 promoter activity [52]. A Bcl-xs plasmid completely abrogated N-nitrosomorpholineinduced HCC formation in Sprague-Dawley rats [54]. A member of the Bcl-2 family, the Bcl-x gene gives rise to two proteins: Bcl-xl, a dominant inhibitor of apoptotic cell death, and Bcl-xs, which promotes apoptosis.…”

Section: Molecular Lesions Underlying Hcc Developmentmentioning

confidence: 99%

Prevention of liver cancer

Guyton

Kensler

2002

Curr Oncol Rep

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is among the most prevalent and deadly cancers worldwide. Prominent risk factors for HCC include viral hepatitis infection; dietary exposure to hepatotoxic contaminants such as aflatoxins; alcoholism; smoking; and male gender. This review highlights ongoing efforts in HCC prevention. Strategies include vaccination against, and treatment of, viral hepatitis infection. In addition to interferon alpha, an acyclic retinoid (all-trans-3,7,11, 15-tetramethyl-2,4,6,10,14-hexadecapentanoic acid), glycyrrhizin and ginseng are currently under clinical investigation for HCC prevention in Japanese hepatitis C patients. Several recent clinical studies in a Chinese region of pervasive aflatoxin contamination also support the approach of favorably altering aflatoxin metabolism and excretion using the chemopreventive agents oltipraz or chlorophyllin. Agents exhibiting chemopreventive efficacy in preclinical HCC models include vitamins A, D, and E, herbal extracts, a 5alpha-reductase inhibitor, green tea, and D-limonene. Efforts to elucidate the molecular lesions and processes underlying HCC development have identified several putative molecular targets for preventive interventions. These include genes and gene products controlling viral replication, carcinogen metabolism, signal transduction, cell-cycle arrest, apoptosis, proliferation, and oxidative stress.

show abstract

Transfer of bcl-xs plasmid is effective in preventing and inhibiting rat hepatocellular carcinoma induced by N-nitrosomorpholine

Cited by 12 publications

References 28 publications

Cyclin L2, a Novel RNA Polymerase II-associated Cyclin, Is Involved in Pre-mRNA Splicing and Induces Apoptosis of Human Hepatocellular Carcinoma Cells

Cyclin L2, a Novel RNA Polymerase II-associated Cyclin, Is Involved in Pre-mRNA Splicing and Induces Apoptosis of Human Hepatocellular Carcinoma Cells

Bak but not Bax is essential for Bcl-xS-induced apoptosis

Prevention of liver cancer

Contact Info

Product

Resources

About