RGD Reference Report - Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts. - Rat Genome Database

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Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer xenografts.

Authors: Anai, S  Goodison, S  Shiverick, K  Iczkowski, K  Tanaka, M  Rosser, CJ 
Citation: Anai S, etal., Hum Gene Ther. 2006 Oct;17(10):975-84.
RGD ID: 2292512
Pubmed: PMID:16984224   (View Abstract at PubMed)
DOI: DOI:10.1089/hum.2006.17.975   (Journal Full-text)

The resistance of prostate cancers to radiation therapy has been linked to abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition of apoptosis. In this study, we evaluated whether the combination of the overexpression of phosphatase and tensin homolog (PTEN), a protein known to inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of athymic mice. Compared with either treatment alone, the combination of adenoviral vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited xenograft tumor growth. Median tumor size on day 48 was 1030 mm3 in untreated controls, 656 mm3 in mice treated with radiation (5 Gy) alone, 640 mm3 in mice treated with AdPTEN alone, and 253 mm3 in mice treated with the combination (p<0.001). Treatment was well tolerated in all cases. Combination treatment also enhanced apoptosis (p=0.048), inhibited cellular proliferation (p=0.005), and inhibited tumor-induced neovascularity (p=0.030). Interestingly, this treatment increased apoptosis not only in tumor cells but also in tumor-associated endothelial cells. Together, these findings indicate that AdPTEN strongly inhibits the growth of human prostate tumors, especially when combined with radiation therapy, and that this effect is mediated by the induction of apoptosis and by the inhibition of angiogenesis and cellular proliferation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer  IDA 2292512 RGD 
prostate cancer  ISOBCL2 (Homo sapiens)2292512; 2292512 RGD 
prostate cancer  IMP 2292512 RGD 
prostate cancer  ISOPTEN (Homo sapiens)2292512; 2292512 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bcl2  (BCL2, apoptosis regulator)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Bcl2  (B cell leukemia/lymphoma 2)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
BCL2  (BCL2 apoptosis regulator)
PTEN  (phosphatase and tensin homolog)


Additional Information