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Series GSE6263

Query DataSets for GSE6263

Status

Public on Nov 15, 2006

Title

Identification of genes whose expression is modulated by the presence or absence of PTEN

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

In an effort to identify genes whose expression is regulated by activated PI3K signaling, we performed microarray analysis and subsequent qRT-PCR on an isogenic set of PTEN gene-targeted human cancer cells. Numerous p53 effectors were upregulated following PTEN deletion, including p21, GDF15, PIG3, NOXA, and PLK2. Stable depletion of p53 led to reversion of the gene expression program. Western blots revealed that p53 was stabilized in HCT116 PTEN-/- cells via an Akt1-dependent and p14ARF-independent mechanism. Stable depletion of PTEN in untransformed human fibroblasts and epithelial cells also led to upregulation of p53 and senescent-like growth arrest. Simultaneous depletion of p53 rescued this phenotype, enabling PTEN-depleted cells to continue proliferating. Next, we tested whether oncogenic PIK3CA, like inactivated PTEN, could activate p53. Retroviral expression of oncogenic human PIK3CA in MCF10A cells led to activation of p53 and upregulation of p53-regulated genes. Stable depletion of p53 reversed these PIK3CA-induced expression changes and synergized with oncogenic PIK3CA in inducing anchorage-independent growth. Finally, targeted deletion of an endogenous allele of oncogenic but not wild-type PIK3CA in a human cancer cell line led to a reduction in p53 levels and a decrease in the expression of p53-regulated genes. These studies demonstrate that activation of PI3K signaling by mutations in PTEN or PIK3CA can lead to activation of p53-mediated growth suppression in human cells, indicating that p53 can function as a brake on PIP3-induced mitogenesis during human cancer pathogenesis.
Keywords: PTEN genotype comparison

Overall design

Two HCT116 PTEN+/+ cell lines (parental cells and a clone with random integration of the targeting vector) and three independently-derived HCT116 PTEN-/- cell lines were studied

Citation(s)

17060456

Submission date

Nov 10, 2006

Last update date

Aug 10, 2018

Contact name

JUNGSIK KIM

E-mail(s)

jk99@georgetown.edu

Organization name

GEORGETOWN UNIVERSITY