Passa al contenuto
Merck
  • Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model.

Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model.

Cancer research (2004-12-03)
Sandra L Krueckl, Robert A Sikes, N Magnus Edlund, Robert H Bell, Antonio Hurtado-Coll, Ladan Fazli, Martin E Gleave, Michael E Cox
ABSTRACT

Apoptosis and inhibition of mitosis are primary mechanisms mediating androgen ablation therapy-induced regression of prostate cancer (PCa). However, PCa readily becomes androgen independent, leading to fatal disease. Up-regulated growth and survival signaling is implicated in development of resistance to androgen ablation therapy. We are testing the hypothesis that insulin-like growth factor (IGF) responsiveness is required for androgen-independent (AI) progression. Using the LNCaP human PCa progression model, we have determined that IGF-I-mediated protection from apoptotic stress and enhanced mitotic activity is androgen dependent in LNCaP cells but is androgen independent in lineage-derived C4-2 cells. Both cell lines exhibit androgen-responsive patterns of IGF-I receptor (IGF-IR) expression, activation, and signaling to insulin receptor substrate-2 and AKT. However, C4-2 cells express higher levels of IGF-IR mRNA and protein and exhibit enhanced IGF-I-mediated phosphorylation and downstream signaling under androgen-deprived conditions. In comparisons of naive and AI metastatic human PCa specimens, we have confirmed that IGF-IR levels are elevated in advanced disease. Together with our LNCaP/C4-2 AI progression model data, these results indicate that increased IGF-IR expression is associated with AI antiapoptotic and promitotic IGF signaling in PCa disease progression.

MATERIALI
N° Catalogo
Marchio
Descrizione del prodotto

Sigma-Aldrich
Anti-phospho-MAP Kinase 1/2 (Erk1/2)(Thr185/Tyr187) Antibody, clone AW39, clone Aw39, Upstate®, from rabbit
Sigma-Aldrich
Anti-IGF-IR (Ab-1) Mouse mAb (αIR3), liquid, clone αIR3, Calbiochem®