Caspase-8 acts as a tumor suppressor in chemically induced hepatocarcinogenesis in mice

Centrosomes are microtubule-organizing centers that facilitate bipolar mitotic spindle assembly and chromosome segregation. Recognizing that centrosome amplification is a common feature of aneuploid cancer cells, we tested whether supernumerary centrosomes are sufficient to drive tumor development. To do this, we constructed and analyzed mice in which centrosome amplification can be induced by a Cre-recombinase–mediated increase in expression of Polo-like kinase 4 (Plk4). Elevated Plk4 in mouse fibroblasts produced supernumerary centrosomes and enhanced the expected mitotic errors, but proliferation continued only after inactivation of the p53 tumor suppressor. Increasing Plk4 levels in mice with functional p53 produced centrosome amplification in liver and skin, but this did not promote spontaneous tumor development in these tissues or enhance the growth of chemically induced skin tumors. In the absence of p53, Plk4 overexpression generated widespread centrosome amplification, but did not drive additional tumors or affect development of the fatal thymic lymphomas that arise in animals lacking p53. We conclude that, independent of p53 status, supernumerary centrosomes are not sufficient to drive tumor formation.

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Somatic Mutation of the Tuberous Sclerosis (Tsc2) Tumor Suppressor Gene in Chemically Induced Rat Renal Carcinoma Cell

The Journal of Urology ◽

10.1097/00005392-199707000-00085 ◽

1997 ◽

Vol 158 (1) ◽

pp. 275-278 ◽

Cited By ~ 26

Author(s):

Shinji Urakami ◽

Reiko Tokuzen ◽

Hiroyuki Tsuda ◽

Mikio Igawa ◽

Okio Hino

Keyword(s):

Tumor Suppressor ◽

Tuberous Sclerosis ◽

Tumor Suppressor Gene ◽

Somatic Mutation ◽

Renal Carcinoma ◽

Carcinoma Cell ◽

Suppressor Gene ◽

Chemically Induced

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The Putative Tumor Suppressor Tsc-22 is Downregulated Early in Chemically Induced Hepatocarcinogenesis and may be a Suppressor of Gadd45b

Toxicological Sciences ◽

10.1093/toxsci/kfm138 ◽

2007 ◽

Vol 99 (1) ◽

pp. 43-50 ◽

Cited By ~ 12

Author(s):

M. Iida ◽

C. H. Anna ◽

N. D. Gaskin ◽

N. J. Walker ◽

T. R. Devereux

Keyword(s):

Tumor Suppressor ◽

Chemically Induced ◽

Putative Tumor Suppressor

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MicroRNA-338-3p Inhibits Proliferation and Promotes Apoptosis of Multiple Myeloma Cells Through Targeting Cyclin-Dependent Kinase 4

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics ◽

10.3727/096504018x15213031799835 ◽

2018 ◽

Vol 27 (1) ◽

pp. 117-124 ◽

Cited By ~ 5

Author(s):

Yang Cao ◽

Xu Shi ◽

Yingmin Liu ◽

Ren Xu ◽

Qing Ai

Keyword(s):

Multiple Myeloma ◽

Tumor Suppressor ◽

Caspase 3 ◽

Biological Role ◽

Algorithm Analysis ◽

Luciferase Reporter ◽

Caspase 8 ◽

Cyclin Dependent Kinase ◽

Multiple Cancer ◽

Cdk4 Expression

MicroRNA-338-3p (miR-338-3p) has been reported to be a tumor suppressor in multiple cancer types. However, the biological role of miR-338-3p and its underlying mechanism in multiple myeloma (MM) remain unclear. In the present study, we investigated the biological role and potential of miR-338-3p in MM. We found that miR-338-3p was significantly decreased in newly diagnosed and relapsed MM tissues and cell lines. Overexpression of miR-338-3p in MM cells significantly inhibited proliferation and promoted apoptosis, caspase 3, and caspase 8 activity. Bioinformatics algorithm analysis predicted that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-338-3p, and this was experimentally verified by a dual-luciferase reporter assay. Furthermore, overexpression of miR-338-3p inhibited CDK4 expression on mRNA and protein levels. Of note, the restoration of CDK4 expression markedly abolished the effect of miR-338-3p overexpression on cell proliferation, apoptosis, caspase 3, and caspase 8 activities in MM cells. Taken together, the present study is the first to demonstrate that miR-338-3p functions as a tumor suppressor in MM through inhibiting CDK4. This finding implies that miR-338-3p is a potential therapeutic target for the treatment of MM.

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Review for "Ablation of spinal cord estrogen receptor α‐expressing interneurons reduces chemically induced modalities of pain and itch"

10.1002/cne.24847/v1/review2 ◽

2019 ◽

Keyword(s):

Spinal Cord ◽

Estrogen Receptor ◽

Estrogen Receptor Α ◽

Chemically Induced

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Biological and Surface Properties of C-Type Virus Particles Produced by Novikoff Ascites Hepatoma Cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100079395 ◽

1977 ◽

Vol 35 ◽

pp. 388-389

Author(s):

D.C. Hixson ◽

J.C. Chan ◽

J.M. Bowen ◽

E.F. Walborg

Keyword(s):

Surface Properties ◽

Ricinus Communis ◽

Rat Kidney ◽

Leukemia Virus ◽

Viral Envelope ◽

Virus Particles ◽

Chemically Induced ◽

Sarcoma Virus ◽

Hepatocarcinoma Cells ◽

Type C

Several years ago Karasaki (1) reported the production of type C virus particles by Novikoff ascites hepatocarcinoma cells. More recently, Weinstein (2) has reported the presence of type C virus particles in cell cultures derived from transplantable and primary hepatocellular carcinomas. To date, the biological function of these virus and their significance in chemically induced hepatocarcinogenesis are unknown. The present studies were initiated to determine a possible role for type C virus particles in chemically induced hepatocarcinogenesis. This communication describes results of studies on the biological and surface properties of type C virus associated with Novikoff hepatocarcinoma cells.Ecotropic and xenotropic murine leukemia virus (MuLV) activity in ascitic fluid of Novikoff tumor-bearing rats was assayed in murine sarcoma virus transformed S+L- mouse cells and S+L- mink cells, respectively. The presence of sarcoma virus activity was assayed in non-virus-producing normal rat kidney (NRK) cells. Ferritin conjugates of concanavalin A (Fer-Con wheat germ agglutinin (Fer-WGA), and Ricinus communis agglutinins I and II (Fer-RCAI and Fer-RCAII) were used to probe the structure and topography of saccharide determinants present on the viral envelope.

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