Growth and gene expression profile analyses of endometrial cancer cells expressing exogenous PTEN.
The PTEN tumor suppressor gene encodes a multifunctional phosphatase that plays an important role in inhibiting the phosphatidylinositol-3-kinase pathway and downstream functions that include activation of Akt/protein kinase B, cell survival, and cell proliferation. Enforced expression of PTEN in various cancer cell lines decreases cell proliferation through arrest of the cell cycle, accompanied in some cases by induction of apoptosis. We used cDNA microarrays containing 4009 cDNAs to examine changes in gene-expression profiles when exogenous PTEN was induced in PTEN-defective cells. The microarrays and subsequent semi-quantitative reverse transcription-PCR analysis revealed transcriptional stimulation of 99 genes and repression of 72 genes. Some of the differentially expressed genes already had been implicated in cell proliferation, differentiation, apoptosis, or cell cycle control, e.g., overexpression of PTEN-induced transactivation of cyclin-dependent inhibitor 1B (p27Kip1) and 2B (p15INK4B), members of the TNF receptor family, tumor necrosis factor-associated genes, and members of the Notch-signaling and Mad families. To our knowledge this is the first report of transactivation of those genes by PTEN. The genes differentially expressed in our experiments also included many whose correlation with cancer development had not been recognized before. Our data should contribute to a greater understanding of the broad spectrum of ways in which PTEN affects intracellular signaling pathways. Analysis of expression profiles with microarrays appears to be a powerful approach for identifying anticancer genes and/or disease-specific targets for cancer therapy.
Matsushima-Nishiu
M
M
Laboratories of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Unoki
M
M
Ono
K
K
Tsunoda
T
T
Minaguchi
T
T
Kuramoto
H
H
Nishida
M
M
Satoh
T
T
Tanaka
T
T
Nakamura
Y
Y
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human