Republication: Targeting PI3KC2β Impairs Proliferation and Survival in Acute Leukemia, Brain Tumours and Neuroendocrine Tumours.

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.

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

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.

Targeting the phosphoinositide 3-kinase isoform p110delta impairs growth and survival in neuroblastoma cells.

Purpose: The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in human cancer and plays a crucial role in neuroblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K/Akt signaling as a novel antiproliferative approach in neuroblastoma.

Experimental Design: The expression pattern and functions of class I(A) PI3K isoforms were investigated in tumor samples and cell lines.

Targeting receptor tyrosine kinase signaling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a quickly progressing, heterogeneous clonal disorder of hematopoietic progenitor cells. Significant progress in understanding the pathogenesis of AML has been achieved in the past few years. Two major types of genetic events are thought to give rise to leukemic transformation: alterations in the activity of transcription factors controlling hematopoietic differentiation and activation of components of receptor tyrosine kinase (RTK) signaling pathways.

Novel role for insulin as an autocrine growth factor for malignant brain tumour cells.

AT/RTs (atypical teratoid/rhabdoid tumours) of the CNS (central nervous system) are childhood malignancies associated with poor survival rates due to resistance to conventional treatments such as chemotherapy. We characterized a panel of human AT/RT and MRT (malignant rhabdoid tumour) cell lines for expression of RTKs (receptor tyrosine kinases) and their involvement in tumour growth and survival. When compared with normal brain tissue, AT/RT cell lines overexpressed the IR (insulin receptor) and the IGFIR (insulin-like growth factor-I receptor).

Recent patents of gene sequences relative to the phosphatidylinositol 3-kinase/Akt pathway and their relevance to drug discovery.

Phosphoinositide 3-kinases (PI3Ks) play an essential role in the signal transduction events initiated by the binding of extracellular signals to their cell surface receptors. There are eight known PI3Ks in humans, which have been subdivided into three classes (I-III). The class I(A) of PI3K comprises the p110alpha, p110beta and p110delta isoforms, which associate with receptor tyrosine kinases (RTKs).

IGF-IR: potential role in antitumor agents.

As insulin-like growth factor (IGF) signaling has been recognized to play an important role in human cancer, the IGF-I receptor (IGF-IR) is currently the focus of intensive research aimed at developing novel antitumor agents. The IGF system is frequently deregulated in cancer cells by the establishment of autocrine loops involving IGF-I or -II and/or IGF-IR over-expression. Moreover, epidemiological studies have suggested a link between elevated IGF levels and the development of major human malignancies, such as breast, colon, lung and prostate cancer.

Diet-dependent effects of the Drosophila Mnk1/Mnk2 homolog Lk6 on growth via eIF4E.

The control of cellular growth is tightly linked to the regulation of protein synthesis. A key function in translation initiation is fulfilled by the 5' cap binding eukaryotic initiation factor 4E (eIF4E), and dysregulation of eIF4E is associated with malignant transformation and tumorigenesis . In mammals, the activity of eIF4E is modulated by phosphorylation at Ser209 by mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1 and Mnk2) , which themselves are activated by ERK and p38 MAPK in response to mitogens, cytokines or cellular stress .