PTEN loss in the continuum of common cancers, rare syndromes and mouse models

MC Hollander, GM Blumenthal, PA Dennis - Nature Reviews Cancer, 2011 - nature.com
MC Hollander, GM Blumenthal, PA Dennis
Nature Reviews Cancer, 2011nature.com
PTEN is among the most frequently inactivated tumour suppressor genes in sporadic
cancer. PTEN has dual protein and lipid phosphatase activity, and its tumour suppressor
activity is dependent on its lipid phosphatase activity, which negatively regulates the PI3K–
AKT–mTOR pathway,. Germline mutations in PTEN have been described in a variety of rare
syndromes that are collectively known as the PTEN hamartoma tumour syndromes (PHTS).
Cowden syndrome is the best-described syndrome within PHTS, with approximately 80% of …
Abstract
PTEN is among the most frequently inactivated tumour suppressor genes in sporadic cancer. PTEN has dual protein and lipid phosphatase activity, and its tumour suppressor activity is dependent on its lipid phosphatase activity, which negatively regulates the PI3K–AKT–mTOR pathway,. Germline mutations in PTEN have been described in a variety of rare syndromes that are collectively known as the PTEN hamartoma tumour syndromes (PHTS). Cowden syndrome is the best-described syndrome within PHTS, with approximately 80% of patients having germline PTEN mutations. Patients with Cowden syndrome have an increased incidence of cancers of the breast, thyroid and endometrium, which correspond to sporadic tumour types that commonly exhibit somatic PTEN inactivation. Pten deletion in mice leads to Cowden syndrome-like phenotypes, and tissue-specific Pten deletion has provided clues to the role of PTEN mutation and loss in specific tumour types. Studying PTEN in the continuum of rare syndromes, common cancers and mouse models provides insight into the role of PTEN in tumorigenesis and will inform targeted drug development.
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