In Vivo Progression of LAPC-9 and LNCaP Prostate Cancer Models to Androgen Independence Is Associated with Increased Expression of Insulin-like Growth Factor I (IGF-I) and IGF-I Receptor (IGF-IR)

摘要: Androgen deprivation therapies for metastatic prostate cancer are useful initially, but progression to androgen independence usually results in relapse within 2 years. The molecular mechanisms underlying the clinically important transition from dependence poorly described. Several lines of investigation have suggested that insulin-like growth factors (IGFs) involved biology cancer, little is known about their relevance independence. We used three vivo models androgen-dependent (AD) human study this issue. Progression androgen-independent (AI) was associated with a 60-fold increase expression IGF-I mRNA LAPC-9 xenografts and 28-fold LNCAP xenografts, relative initial AD neoplasms. IGF type I receptor (IGF-IR) levels were ∼2.5-fold ∼5-fold higher, respectively, AI LNCaP tumors compared original these also significant reductions binding protein-3 expression. LAPC-4 which previously been shown exhibit pathology related HER-2/neu AI, showed relatively minor changes genes investigated, we nevertheless found evidence increased IGF-IR phosphorylation model. Taken together prior observations, our suggest deregulation any one several critical tyrosine kinase regulatory systems, including signaling, may confer