RGD Reference Report - Expression of p16(INK4A) induces dominant suppression of glioblastoma growth in situ through necrosis and cell cycle arrest. - Rat Genome Database

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Expression of p16(INK4A) induces dominant suppression of glioblastoma growth in situ through necrosis and cell cycle arrest.

Authors: Hung, KS  Hong, CY  Lee, J  Lin, SK  Huang, SC  Wang, TM  Tse, V  Sliverberg, GD  Weng, SC  Hsiao, M 
Citation: Hung KS, etal., Biochem Biophys Res Commun. 2000 Mar 24;269(3):718-25.
RGD ID: 8552659
Pubmed: PMID:10720483   (View Abstract at PubMed)
DOI: DOI:10.1006/bbrc.2000.2339   (Journal Full-text)

Tumor suppressor genes may represent an important new therapeutic modality in the treatment of human glioblastoma (GBM). p16(INK4A) is a tumor suppressor gene with mutation and/or deletion found in many human tumors, including glioblastomas, melanoma, and leukemias. RT-2 rat GBM cell line was used to investigate if the p16 gene induces dominant suppression of glioblastoma growth. Close to 100% of tumor cells were infected by high titer pCL retrovirus encoding the full-length human p16 cDNA at 5 m.o.i. Infected cells showed a 98% reduction in colony forming assay and a 60% reduction in growth curves in vitro compared to vector control. Exogenous overexpression of p16 induced hypophosphorylation of Rb protein by Western blot analysis. Intracranial injection of p16-infected tumor cells into syngeneic rats resulted in a 95% reduction in tumor volume compared to the controls. Intratumoral injection of p16 retrovirus resulted in tumor necrosis and prominent human p16 transgene expressions. Proliferation marker PCNA was not detected in these human p16-expressed RT-2 tumor cells, suggesting the cells were unable to enter into S phase after p16 expression. In addition, direct repeat intracranial injections of p16 retrovirus prolonged animal survival 3.2-fold compared to the controls (48.4 +/- 13.4 vs 15.0 +/- 2.1 days, p < 0.001). Two out of ten rats were found with dormant tumors at day 60 after p16 retrovirus injection. These results showed that p16 is effective in inhibiting GBM growth in situ. The mechanisms of tumor growth reduction and necrosis in vivo might be due to G1 arrest triggered by p16 expression.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
CDKN2AHumanglioblastoma treatmentIMP  RGD 
Cdkn2aRatglioblastoma treatmentISOCDKN2A (Homo sapiens) RGD 
Cdkn2aMouseglioblastoma treatmentISOCDKN2A (Homo sapiens) RGD 
Cdkn2a_v1Ratglioblastoma treatmentISOCDKN2A (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdkn2a  (cyclin-dependent kinase inhibitor 2A)
Cdkn2a_v1  (cyclin-dependent kinase inhibitor 2A, variant 1)

Genes (Mus musculus)
Cdkn2a  (cyclin dependent kinase inhibitor 2A)

Genes (Homo sapiens)
CDKN2A  (cyclin dependent kinase inhibitor 2A)


Additional Information