Targeting PI3KC2β impairs proliferation and survival in acute leukemia, brain tumours and neuroendocrine tumours.

Abstract

BACKGROUND:

Eight human catalytic phosphoinositide 3-kinase (PI3K) isoforms exist which are subdivided into three classes. While class I isoforms have been well-studied in cancer, little is known about the functions of class II PI3Ks.

MATERIALS AND METHODS:

The expression pattern and functions of the class II PI3KC2β isoform were investigated in a panel of tumour samples and cell lines.

RESULTS:

Overexpression of PI3KC2β was found in subsets of tumours and cell lines from acute myeloid leukemia (AML), glioblastoma multiforme (GBM), medulloblastoma (MB), neuroblastoma (NB), and small cell lung cancer (SCLC). Specific pharmacological inhibitors of PI3KC2β or RNA interference impaired proliferation of a panel of human cancer cell lines and primary cultures. Inhibition of PI3KC2β also induced apoptosis and sensitised the cancer cells to chemotherapeutic agents.

CONCLUSION:

Together, these data show that PI3KC2β contributes to proliferation and survival in AML, brain tumours and neuroendocrine tumours, and may represent a novel target in these malignancies.

• Authors: Danielle Boller, Kathrin T Doepfner, Angela De Laurentiis, Ana S Guerreiro, Marin Marinov, Tarek Shalaby, Paul Depledge, Anthony Robson, Nahid Saghir, Masahiko Hayakawa, Hiroyuki Kaizawa, Tomonobu Koizumi, Takahide Ohishi, Sarah Fattet, Olivier Delattre, Anelia Schweri-Olac, Katrin Höland, Michael A Grotzer, Karl Frei, Olivier Spertini, Michael D Waterfield, Alexandre Arcaro
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 8 Pg. 3015-27 (08 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 22843869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Enzyme Inhibitors
• Isoenzymes
• Phosphoinositide-3 Kinase Inhibitors

Topics

• Animals
• Brain Neoplasms (pathology)
• Cell Line, Tumor
• Cell Proliferation
• Electrophoresis, Polyacrylamide Gel
• Enzyme Inhibitors (pharmacology)
• Humans
• Inhibitory Concentration 50
• Isoenzymes (metabolism)
• Leukemia, Myeloid, Acute (pathology)
• Mice
• Neuroendocrine Tumors (pathology)
• Oligonucleotide Array Sequence Analysis
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoinositide-3 Kinase Inhibitors
• Survival Rate