Skip to main content



Buy Article:

$51.00 plus tax (Refund Policy)

Abstract:

Lens Epithelium-Derived Growth Factor (LEDGF/p75) is a transcriptional co-activator and survival factor in lens epithelium cells (LECs) where it regulates small heat shock proteins (Hsp27 and β-crystalin) and confers resistance to a variety of stress insults including oxidative- and heat stress. We have recently cloned LEDGF/p75 as an Hsp70–2 regulated survival factor in human cancer and shown that it protects epithelial cancer cells from the drug-induced activation of an alternative apoptosis-like cell death pathway that involves destabilization of lysosomes. By using a stable cell line over-expressing LEDGF/p75 we here show that LEDGF/p75 protect cancer cells from cell death induced by a new potential cancer drug named bLAC (bovine α- Lact Albumin Complex) and significantly increases the long-term colony-forming ability of cancer cells after treatment with the lysosome destabilizing drug siramesine. The mechanism by which LEDGF/p75 exerts its survival effect is still unknown but since LEDGF/p75 localize to the nucleus we reasoned that LEDGF/p75 is likely to affect transcription. In a real-time PCR analysis of potential LEDGF/p75 target genes in cancer we failed to see the LEDGF/p75-dependent regulation of small Hsps as evident in LECs. However, ectopic over-expression of LEDGF/p75 promotes a transcriptional up-regulation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) decoy receptor (DcR2) that is deregulated in several types of cancer and promotes cell survival by neutralizing pro-apoptotic TRAIL-ligand. Importantly and contrary to enforced LEDGF/p75 expression, RNAi-mediated knockdown of LEDGF leads to down-regulation of the DcR2 mRNA suggesting that DcR2 is under direct transcriptional control of LEDGF/p75. Whether DcR2 plays a role in LEDGF/p75-mediated cancer cell survival remains to be elucidated.

Document Type: Abstract

DOI: http://dx.doi.org/10.1111/j.1600-0463.2008.001165_4.x

Affiliations: 1: Apoptoselaboratoriet, Institut for Biologisk Kræftforskning, Kræftens Bekæmpelse, Strandboulevarden 49 2: NatImmune A/S, Symbion Science Park, Fruebjergvej 3, 2100 København Ø

Publication date: May 1, 2008

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Partial Open Access Content
Partial Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more