PMID- 10362360
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20161124
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 22
DP  - 1999 Jun 3
TI  - Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells 
      from apoptosis induced by photodynamic therapy or thapsigargin.
PG  - 3391-8
AB  - Prostate carcinoma (PCA) is the most frequently diagnosed malignancy in American 
      men. PCA at advanced stages can both proliferate abnormally and resist apoptosis. 
      Among the many known signal transduction pathways, phosphatidylinositide-3'OH 
      kinase (PI3-kinase) has been shown to play an important role in cell survival and 
      resistance to apoptosis. In this study, we investigate the involvement of 
      Etk/Bmx, a newly discovered tyrosine kinase that is a substrate of PI3-kinase, in 
      protection of prostate cancer cells from apoptosis. Parental LNCaP cells and two 
      derivative cell lines, one overexpressing wild type Etk (Etkwt) and the other 
      expressing a dominant negative Etk (EtkDN), were used to study the function of 
      Etk. The cells were treated with photodynamic therapy (PDT), a newly approved 
      cancer treatment which employs a photosensitizer and visible light to produce an 
      oxidative stress in cells, often leading to apoptosis. Our results indicate that 
      PDT induces apoptosis in LNCaP cells, as measured by DNA fragmentation and by 
      cleavage of poly(ADP-ribose) polymerase (PARP), and moreover, the extent of 
      apoptosis was much reduced in Etkwt cells as compared to LNCaP or EtkDN cells. 
      Assay of overall cell viability confirmed that Etkwt cells were considerably less 
      sensitive to PDT than were the parental LNCaP or EtkDN cells. Similar results 
      were found in response to thapsigargin (TG). A specific inhibitor of PI3-kinase, 
      LY294002, abolished Etk activity and markedly increased TG-induced PARP cleavage. 
      The results suggest that Etk/Bmx is an efficient effector of PI3-kinase and that 
      the newly described PI3-kinase/Etk pathway is involved in the protection of 
      prostate carcinoma cells from apoptosis in response to PDT or TG.
FAU - Xue, L Y
AU  - Xue LY
AD  - Department of Radiation Oncology, Case Western Reserve University School of 
      Medicine, Cleveland, Ohio 44106, USA.
FAU - Qiu, Y
AU  - Qiu Y
FAU - He, J
AU  - He J
FAU - Kung, H J
AU  - Kung HJ
FAU - Oleinick, N L
AU  - Oleinick NL
LA  - eng
GR  - CA39207/CA/NCI NIH HHS/United States
GR  - CA57179/CA/NCI NIH HHS/United States
GR  - P01 CA48735/CA/NCI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (Photosensitizing Agents)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.1.- (BMX protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Apoptosis/drug effects/*physiology
MH  - Carcinoma/*drug therapy/enzymology/pathology
MH  - Cell Survival/drug effects
MH  - Chromones/pharmacology
MH  - DNA Fragmentation/drug effects
MH  - Enzyme Inhibitors/*pharmacology
MH  - Humans
MH  - Male
MH  - Morpholines/pharmacology
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Photochemotherapy
MH  - Photosensitizing Agents/pharmacology
MH  - Poly(ADP-ribose) Polymerases/drug effects/metabolism
MH  - Prostatic Neoplasms/*drug therapy/enzymology/pathology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Thapsigargin/*pharmacology
MH  - Tumor Cells, Cultured/drug effects/metabolism
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1038/sj.onc.1202687 [doi]
PST - ppublish
SO  - Oncogene. 1999 Jun 3;18(22):3391-8. doi: 10.1038/sj.onc.1202687.