title: Targeting PI3KC2β impairs proliferation and survival in acute leukemia, brain tumours and neuroendocrine tumours.
abstract: 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.
  
  
  
  The expression pattern and functions of the class II PI3KC2β isoform were investigated in a panel of tumour samples and cell lines.
  
  
  
  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.
  
  
  
  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: Division of Clinical Chemistry and Biochemistry, University Children’s Hospital Zurich, Zurich, Switzerland.
authors: Danielle
authors: D
authors: Boller
authors: Kathrin T
authors: KT
authors: Doepfner
authors: Angela
authors: A
authors: De Laurentiis
authors: Ana S
authors: AS
authors: Guerreiro
authors: Marin
authors: M
authors: Marinov
authors: Tarek
authors: T
authors: Shalaby
authors: Paul
authors: P
authors: Depledge
authors: Anthony
authors: A
authors: Robson
authors: Nahid
authors: N
authors: Saghir
authors: Masahiko
authors: M
authors: Hayakawa
authors: Hiroyuki
authors: H
authors: Kaizawa
authors: Tomonobu
authors: T
authors: Koizumi
authors: Takahide
authors: T
authors: Ohishi
authors: Sarah
authors: S
authors: Fattet
authors: Olivier
authors: O
authors: Delattre
authors: Anelia
authors: A
authors: Schweri-Olac
authors: Katrin
authors: K
authors: Höland
authors: Michael A
authors: MA
authors: Grotzer
authors: Karl
authors: K
authors: Frei
authors: Olivier
authors: O
authors: Spertini
authors: Michael D
authors: MD
authors: Waterfield
authors: Alexandre
authors: A
authors: Arcaro
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D051379:Mice; D018358:Neuroendocrine Tumors / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015996:Survival Rate
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors