RGD Reference Report - Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors. - Rat Genome Database

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Activated mammalian target of rapamycin pathway in the pathogenesis of tuberous sclerosis complex renal tumors.

Authors: Kenerson, HL  Aicher, LD  True, LD  Yeung, RS 
Citation: Kenerson HL, etal., Cancer Res 2002 Oct 15;62(20):5645-50.
RGD ID: 1549429
Pubmed: PMID:12384518   (View Abstract at PubMed)

Disruption of the TSC1 or TSC2 gene leads to the development of tumors in multiple organs, most commonly affecting the kidney, brain, lung, and heart. Recent genetic and biochemical studies have identified a role for the tuberous sclerosis gene products in phosphoinositide 3-kinase signaling. On growth factor stimulation, tuberin, the TSC2 protein, is phosphorylated by Akt, thereby releasing its inhibitory effects on p70S6K. Here we demonstrate that primary tumors from tuberous sclerosis complex (TSC) patients and the Eker rat model of TSC expressed elevated levels of phosphorylated mammalian target of rapamycin (mTOR) and its effectors: p70S6K, S6 ribosomal protein, 4E-BP1, and eIF4G. In the Eker rat, short-term inhibition of mTOR by rapamycin was associated with a significant tumor response, including induction of apoptosis and reduction in cell proliferation. Surprisingly, these changes were not accompanied by significant alteration in cyclin D1 and p27 levels. Our data provide in vivo evidence that the mTOR pathway is aberrantly activated in TSC renal pathology and that treatment with rapamycin appears effective in the preclinical setting.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tuberous sclerosis treatmentISOEif4ebp1 (Rattus norvegicus)1549429; 1549429 RGD 
tuberous sclerosis treatmentIDA 1549429 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eif4ebp1  (eukaryotic translation initiation factor 4E binding protein 1)

Genes (Mus musculus)
Eif4ebp1  (eukaryotic translation initiation factor 4E binding protein 1)

Genes (Homo sapiens)
EIF4EBP1  (eukaryotic translation initiation factor 4E binding protein 1)


Additional Information