Id-1 expression promotes cell survival through activation of NF-κB signalling pathway in prostate cancer cells

Abstract

The growth-promoting effect of Id-1 (inhibitor of differentiation/DNA binding) has been demonstrated in a number of human cancers. However, the mechanisms responsible for its action are not clear. In this study, we report that in prostate cancer cells, Id-1 promotes cell survival through activation of nuclear factor-jB (NF-jB) signalling pathway. After stable expression of Id-1 protein in LNCaP cells, we found that the Id-1 transfectants showed increased resistance to apoptosis induced by TNFa through inactivation of Bax and caspase 3. In addition, in the LNCaP cells expressing ectopic Id-1 protein, we also observed increased NF-jB transactivation activity and nuclear translocation of the p65 and p50 proteins, which was accompanied by upregulation of their downstream effectors Bcl-xL and ICAM-1. These results indicate that the Id-1-induced antiapoptotic effect may be via NF-jB signalling transduction pathway in these cells. In addition, inactivation of Id-1 by its antisense oligonucleotide and retroviral construct in DU145 cells resulted in the decrease of nuclear level of p65 and p50 proteins, which was associated with increased sensitivity to TNFa-induced apoptosis. Our results strongly suggest that Id-1 may be one of the upstream regulators of NF-jB and activation of NF-jB signalling pathway may be essential for Id-1 induced cell proliferation through protection against apoptosis. Our findings also suggest a potential therapeutic strategy in which inactivation of Id-1 may lead to sensitization of prostate cancer cells to chemotherapeutic drug-induced apoptosis.

Reassessment of Id1 Protein Expression in Human Mammary, Prostate, and Bladder Cancers Using a Monospecific Rabbit Monoclonal Anti-Id1 Antibody

“…Mobilization of endothelial cell progenitors from the bone marrow is also severely perturbed in Id knockout mice consistent with this hypothesis (10,11). On the other hand, a role for Id1 in modulating tumor epithelial cell behavior is suggested by the fact that overexpression of Id1 in cell lines results in increased invasiveness and metastatic potential of these cells, whereas reduction of high levels of Id1 present endogenously in these lines leads to an inhibition of these properties (12)(13)(14)(15)(16)(17).…”

Over-expression of Id2 and Id3 Proteins Regulates Growth and Survival of Human Colon Carcinoma (HCT116) Cells

“…Apoptosis induction by Id proteins has been found to be complex in different variety of cell types [16]. However, Id proteins have been shown to have antiapoptotic activity [17] as observed with Id2 in this study.…”

Interference of the dominant negative helix–loop–helix protein ID1 with the proteasomal subunit S5A causes centrosomal abnormalities

“…ID proteins form DNA-binding incompetent heterodimers with bHLH transcription factors thereby inhibiting their transcriptional activities (Benezra et al, 1990). Individual ID-proteins have been linked to inhibiting cellular differentiation, inhibition of bHLHand other transcription factors (Benezra et al, 1990;Jen et al, 1992;Kreider et al, 1992;Ohtani et al, 2001;Roberts et al, 2001), modulating apoptosis (Florio et al, 1998;Ling et al, 2003), cooperating with the retinoblastoma tumor suppressor pathway (Iavarone et al, 1994;Hara et al, 1996), extending cellular life span (Alani et al, 1999;Nickoloff et al, 2000;Tang et al, 2002), regulating angiogenesis (Lyden et al, 2001) as well as cardiac development (Fraidenraich et al, 2004), and stem cell maintenance (Ying et al, 2003). ID expression is induced as part of the immediate-early transcriptional response to growth factors and is regulated in a cell cycle-dependent manner.…”