TY - JOUR
T1 - Non-genomic loss of PTEN function in cancer
T2 - not in my genes
AU - Leslie, Nicholas R
AU - Foti, Michelangelo
N1 - Copyright © 2010 Elsevier Ltd. All rights reserved.
PY - 2011/3
Y1 - 2011/3
N2 - Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice with reductions in PTEN gene dosage indicate that even partial loss of PTEN function is sufficient to promote some cancer types, particularly in the breast. PTEN expression appears to be tightly controlled both transcriptionally and post-transcriptionally, with several recent studies implicating oncogenic microRNAs in PTEN suppression. The lipid phosphatase activity of PTEN can also be regulated post-translationally via inhibitory phosphorylation, ubiquitination or oxidation. Here we discuss these multiple mechanisms of PTEN regulation. We also put into context recent proposals that changes in this regulation can drive tumour development and address the accompanying evidence for their clinical significance.
AB - Loss of function of the phosphatase and tensin homolog (PTEN) tumour suppressor contributes to the development of many cancers. However, in contrast to classical models of tumour suppression, partial loss of PTEN function appears to be frequently observed in the clinic. In addition, studies of both humans and mice with reductions in PTEN gene dosage indicate that even partial loss of PTEN function is sufficient to promote some cancer types, particularly in the breast. PTEN expression appears to be tightly controlled both transcriptionally and post-transcriptionally, with several recent studies implicating oncogenic microRNAs in PTEN suppression. The lipid phosphatase activity of PTEN can also be regulated post-translationally via inhibitory phosphorylation, ubiquitination or oxidation. Here we discuss these multiple mechanisms of PTEN regulation. We also put into context recent proposals that changes in this regulation can drive tumour development and address the accompanying evidence for their clinical significance.
U2 - 10.1016/j.tips.2010.12.005
DO - 10.1016/j.tips.2010.12.005
M3 - Article
C2 - 21236500
SN - 0165-6147
VL - 32
SP - 131
EP - 140
JO - Trends in Pharmacological Sciences
JF - Trends in Pharmacological Sciences
IS - 3
ER -