mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways

Majumder PK, Febbo PG, Bikoff R, Berger R, Xue Q, McMahon LM, Manola J, Brugarolas J, McDonnell TJ, Golub TR, Loda M, …, Sellers WR · 2004 · Nature medicine · Atlas ID MAJ2004

What this study shows

mTOR inhibition (rapamycin/RAD001) reverses Akt-driven prostate intraepithelial neoplasia in mice.

Abstract

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Loss of PTEN function leads to activation of phosphoinositide 3-kinase (PI3K) signaling and Akt. Clinical trials are now testing whether mammalian target of rapamycin (mTOR) inhibition is useful in treating PTEN-null cancers. Here, we report that mTOR inhibition induced apoptosis of epithelial cells and the complete reversal of a neoplastic phenotype in the prostate of mice expressing human AKT1 in the ventral prostate. Induction of cell death required the mitochondrial pathway, as prostate-specific coexpression of BCL2 blocked apoptosis.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (prostate)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (prostate)
Journal	Nature medicine
Year	2004
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/nm1052 · PMID 15156201

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	mTOR inhibition (rapamycin)
Target	mTOR / Akt / HIF-1
Model	Mouse (prostate, AKT1 transgenic)
Effect	mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia via apoptotic and HIF-1-dependent pathways

In the Atlas

Links in the pathway map

Supports mTORC1 activates Prostate cancer
Supports mTORC1 activates HIF-1α

Cite this paper

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Majumder, P. K., Febbo, P. G., Bikoff, R., Berger, R., Xue, Q., McMahon, L. M., Manola, J., Brugarolas, J., McDonnell, T. J., Golub, T. R., Loda, M., Lane, H. A., & Sellers, W. R. (2004). mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nature medicine. https://doi.org/10.1038/nm1052

@article{MAJ2004,
  author       = {Majumder, P. K. and Febbo, P. G. and Bikoff, R. and Berger, R. and Xue, Q. and McMahon, L. M. and Manola, J. and Brugarolas, J. and McDonnell, T. J. and Golub, T. R. and Loda, M. and Lane, H. A. and Sellers, W. R.},
  title        = {{mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways}},
  journal      = {Nature medicine},
  year         = {2004},
  doi          = {10.1038/nm1052},
  note         = {PMID: 15156201},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record MAJ2004) [Data set]. https://mtor-atlas.org/study/MAJ2004/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MAJ2004,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MAJ2004},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MAJ2004/},
  doi          = {10.5281/zenodo.22059963}
}

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