Sex steroids upregulate the IGF-1R in prostate cancer cells through a nongenotropic pathway

Giuseppe Pandini, Marco Genua, Francesco Frasca, Riccardo Vigneri, Antonino Belfiore

Research output: Chapter in Book/Report/Conference proceedingConference contribution


Most types of prostate cancer (PCa) are usually initially responsive to androgenic regulation and, therefore, to androgen ablation therapy. However, in several patients tumors may progress to androgen resistance and be poorly responsive to any therapy. Many factors may account for this progression to androgen independence, including increased responsiveness to estrogens and peptide growth factors. The role of estrogens in androgen independence has been suggested by the observation that both primary and metastatic PCa express the estrogen receptor (ER-β), a recently discovered ER subtype. On the other hand, peptide growth factors, like IGF-1, IGF-2, and the insulin-like growth factor receptor (IGF-1R), may play a role in regulating growth, survival, and invasion of PCa cells. Here, we show that both androgens and estrogens markedly upregulate the IGF-1R expression in PCa cells by activating a nongenotropic pathway and sensitizing cells to the biological effects of IGF-1. This effect is specific for IGF-1R because it does not involve the highly homologous insulin receptor. IGF-1R upregulation is caused by increased mRNA transcription. However, it does not require steroid receptor binding to DNA, but involves AR and ER binding to c-Src and subsequent activation of ERK1/2 and other cytoplasmatic kinases, which eventually stimulate IGF-1R promoter activity. In conclusion, our data indicate that both androgens and estrogens contribute to IGF system deregulation in PCa and may play a role in tumor progression to androgen independence. Inhibition of the IGF-1R or the Src-ERK pathway should be considered, therefore, as an adjuvant therapy in PCa.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Number of pages5
Publication statusPublished - Feb 2009

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)00778923
ISSN (Electronic)17496632


  • Androgen
  • Estrogen
  • Insulin-like growth factor (IGF)-1 receptor
  • Prostate cancer (PCa)

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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