Pml represses tumour progression through inhibition of mTOR

Rosa Bernardi, Antonella Papa, Ainara Egia, Nadia Coltella, Julie Teruya-Feldstein, Sabina Signoretti, Pier Paolo Pandolfi

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14 Citations (Scopus)

Abstract

The promyelocytic leukaemia gene PML is a pleiotropic tumour suppressor. We have recently demonstrated that PML opposes mTOR-HIF1α-VEGF signalling in hypoxia. To determine the relevance of PML-mTOR antagonism in tumourigenesis, we have intercrossed Pml null mice with Tsc2 heterozygous mice, which develop kidney cysts and carcinomas exhibiting mTOR upregulation. We find that combined inactivation of Pml and Tsc2 results in aberrant TORC1 activity both in pre-tumoural kidneys as well as in kidney lesions. Such increase correlates with a marked acceleration in tumour progression, impacting on both the biology and histology of kidney carcinomas. Also, Pml inactivation decreases the rate of loss of heterozygosity (LOH) for the wt Tsc2 allele. Interestingly, however, aberrant TORC1 activity does not accelerate renal cystogenesis in Tsc2/Pml mutants. Our data demonstrate that activation of mTOR is critical for tumour progression, but not for tumour initiation in the kidney.

Original languageEnglish
Pages (from-to)249-257
Number of pages9
JournalEMBO Molecular Medicine
Volume3
Issue number5
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Keywords

  • Cyst
  • Kidney
  • MTOR
  • PML
  • Tumour

Cite this

Bernardi, R., Papa, A., Egia, A., Coltella, N., Teruya-Feldstein, J., Signoretti, S., & Pandolfi, P. P. (2011). Pml represses tumour progression through inhibition of mTOR. EMBO Molecular Medicine, 3(5), 249-257. https://doi.org/10.1002/emmm.201100130