Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling by array of human prostate cancer cells enriched for cell surface markers CD44/CD133/alpha 2 beta 1 integrin

ABSTRACT: Self-renewing tumor initiating cells that are capable of differentiation and responsible for tumor growth have been isolated from cancers and cell lines. If such minor populations are associated with tumor progression, understanding molecular pathways that are required for viability and maintenance of these populations will allow to target these pathways to eradicate tumors that are resistant to existing therapies. In this study we enriched for prostate cancer progenitors (Pr. CPM-CM-"M-BM-^@M-BM-^Ys) expressing cell surface markers CD44/CD133/alpha 2 beta 1 integrin in non-adherent serum-free growth conditions maintained as spheres. Cells grown in these conditions have increased in vivo clonogenic and in vivo tumorigenic potential. microarray analysis of cells grown in sphere conditions compared with long term monolayer culture conditions revealed preferential activation of PI3K/AKT pathway in prostate cancer progenitors. PI3K p110 alpha and beta protein levels were high in sphere condition cultured cells, and PTEN knockdown lead to an increase in Pr.CPM-CM-"M-BM-^@M-BM-^Ys, and to increased clonogenic and tumorigenic potential. Inhibition of Akt1 phosphorylation target FoxO3a lead to inhibition of tumorigenic capacity in vivo for prostate cancer cells. Inhibition of PI3K activity by PI3K inhibitor NVP-BEZ235 lead to a selective inhibition of Pr.CPM-CM-"M-BM-^@M-BM-^Ys, nuclear localization of FoxO3a and increase in GADD45a in prostate cancer cells. Taken together our data strongly suggest that PTEN and PI3K/Akt pathways are critical for prostate cancer stem-like cell maintenance and targeting the PI3K signaling by selective inhibitors may give an incredible advancement in prostate cancer treatment. Experiment Overall Design: sphere and monolayer cultures from two different prostate cancer cell lines

ORGANISM(S): Homo sapiens

SUBMITTER: John Walker

PROVIDER: E-GEOD-10832 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations.

Dubrovska Anna A Kim Sungeun S Salamone Richard J RJ Walker John R JR Maira Sauveur-Michel SM García-Echeverría Carlos C Schultz Peter G PG Reddy Venkateshwar A VA

Proceedings of the National Academy of Sciences of the United States of America 20081230 1

Characterization of the molecular pathways that are required for the viability and maintenance of self-renewing tumor-initiating cells may ultimately lead to improved therapies for cancer. In this study, we show that a CD133(+)/CD44(+) population of cells enriched in prostate cancer progenitors (PCaPs) has tumor-initiating potential and that these progenitors can be expanded under nonadherent, serum-free, sphere-forming conditions. Cells grown under these conditions have increased in vitro clono ...[more]

PMID: 19116269

Publication: 1/2

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Dataset Information

Transcription profiling by array of human prostate cancer cells enriched for cell surface markers CD44/CD133/alpha 2 beta 1 integrin

Publications

The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations.

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