Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR

Neshat MS, Mellinghoff IK, Tran C, Stiles B, Thomas G, Petersen R, Frost P, Gibbons JJ, Wu H, Sawyers CL · 2001 · PNAS · Atlas ID NES2001

What this study shows

Tested whether tumour cells that have lost PTEN depend more on mTOR. The rapamycin analogue CCI-779 (temsirolimus) blocked growth of PTEN-null cells and tumours preferentially, and reversed the extra tumour growth caused by constitutively active Akt, placing mTOR downstream of Akt in tumour formation. PTEN loss went with higher S6 kinase activity and S6 phosphorylation. Sensitivity was not explained by how well the drug blocked S6 phosphorylation, since S6 was inhibited in sensitive and resistant lines alike. Boundary: worked from the abstract only (scanned PMC record); mouse and human cell lines and mouse tumour models, not patients.

Abstract

ShowHide

Recent evidence places the FRAP/mTOR kinase downstream of the phosphatidyl inositol 3-kinase/Akt-signaling pathway, which is up-regulated in multiple cancers because of loss of the PTEN tumor suppressor gene. We performed biological and biochemical studies to determine whether PTEN-deficient cancer cells are sensitive to pharmacologic inhibition of FRAP/mTOR by using the rapamycin derivative CCI-779.

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: Isogenic PTEN+/+ and PTEN-/- mouse cells and human cancer cell lines, in vitro and as tumours in mice; CCI-779); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Isogenic PTEN+/+ and PTEN-/- mouse cells and human cancer cell lines, in vitro and as tumours in mice; CCI-779
Journal	PNAS
Year	2001
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1073/pnas.171076798 · PMID 11504908 · Free full text (PMC56958)

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	CCI-779 (temsirolimus); PTEN loss; constitutively active Akt
Target	PTEN/Akt -> mTOR
Model	Mouse cells, human cancer cell lines, mouse tumour models
Effect	PTEN-null tumours are preferentially growth-inhibited by mTOR inhibition

In the Atlas

Links in the pathway map

Supports mTORC1 activates Tumor growth

Cite this paper

ShowHide

Neshat, M. S., Mellinghoff, I. K., Tran, C., Stiles, B., Thomas, G., Petersen, R., Frost, P., Gibbons, J. J., Wu, H., & Sawyers, C. L. (2001). Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. PNAS. https://doi.org/10.1073/pnas.171076798

@article{NES2001,
  author       = {Neshat, M. S. and Mellinghoff, I. K. and Tran, C. and Stiles, B. and Thomas, G. and Petersen, R. and Frost, P. and Gibbons, J. J. and Wu, H. and Sawyers, C. L.},
  title        = {{Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR}},
  journal      = {PNAS},
  year         = {2001},
  doi          = {10.1073/pnas.171076798},
  note         = {PMID: 11504908},
}

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 NES2001) [Data set]. https://mtor-atlas.org/study/NES2001/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_NES2001,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record NES2001},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/NES2001/},
  doi          = {10.5281/zenodo.22059963}
}

Was this page useful?