RGD Reference Report - Regulation of PI 3-K, PTEN, p53, and mTOR in Malignant and Benign Tumors Deficient in Tuberin. - Rat Genome Database

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Regulation of PI 3-K, PTEN, p53, and mTOR in Malignant and Benign Tumors Deficient in Tuberin.

Authors: Habib, Samy L  Yadav, Anamika  Mahimainathan, Lenin  Valente, Anthony J 
Citation: Habib SL, etal., Genes Cancer. 2011 Nov;2(11):1051-60. doi: 10.1177/1947601912445376.
RGD ID: 12802360
Pubmed: (View Article at PubMed) PMID:22737271
DOI: Full-text: DOI:10.1177/1947601912445376

The tuberous sclerosis complex (TSC) is caused by mutation in either of 2 tumor suppressor genes, TSC-1 (encodes hamartin) and TSC-2 (encodes tuberin). In humans, deficiency in TSC1/2 is associated with benign tumors in many organs, including renal angiomyolipoma (AML) but rarely renal cell carcinoma (RCC). In contrast, deficiency of TSC function in the Eker rat is associated with RCC. Here, we have investigated the activity of PI 3-K and the expression of PTEN, p53, tuberin, p-mTOR, and p-p70S6K in both Eker rat RCC and human renal AML. Compared to normal tissue, increased PI 3-K activity was detected in RCC of Eker rats but not in human AML tissue. In contrast, PTEN was highly expressed in AML but significantly reduced in the renal tumors of Eker rats. Phosphorylation on Ser(2448) of mTOR and Thr(389) of p70S6K were significantly increased in both RCC and AML compared to matching control tissue. Total tuberin was significantly decreased in AML while completely lost in RCC of Eker rats. Our data also show that while p53 protein expression is lost in rat RCC, it was highly elevated in AML. These novel data provide evidence that loss of TSC-2, PTEN, and p53 as well as activation of PI 3-K and mTOR is associated with kidney cancer in the Eker rat, while sustained expression of TSC-2, PTEN, and p53 may prevent progression of kidney cancer in TSC patients.


Disease Annotations    
angiomyolipoma  (IEP,ISO)
renal cell carcinoma  (IEP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Pten  (phosphatase and tensin homolog)

Genes (Mus musculus)
Pten  (phosphatase and tensin homolog)

Genes (Homo sapiens)
PTEN  (phosphatase and tensin homolog)

Additional Information