Targeted deletion of hepatic Igf1 in TRAMP mice leads to dramatic alterations in the circulating insulin-like growth factor axis but does not reduce tumor progression

Makoto Anzo, Laura J. Cobb, David L. Hwang, Hemal Mehta, Jonathan W. Said, Shoshana Yakar, Derek LeRoith, Pinchas Cohen

Research output: Contribution to journalArticle


The role of systemic and local insulin-like growth factor I (IGF-I) in the development of prostate cancer is still controversial. Transgenic adenocarcinoma mouse prostate (TRAMP) mice express the SV40 T-antigen under the control of the probasin promoter, and spontaneously develop prostate cancer. We crossed TRAMP mice with liver IGF-deficient (LID) mice to produce LID-TRAMP mice, a mouse model of prostate cancer with low serum IGF-I, to allow us to study the effect of circulatory IGF-I levels on the development of prostate cancer. LID mice have a targeted deletion of the hepatic Igf1 gene but retain normal expression of Igf1 in extrahepatic tissues. Serum IGF-I and IGFBP-3 levels in LID and LID-TRAMP mice were measured using novel assays, which showed that they are ∼10% and 60% of control L/L- mice, respectively. Serum growth hormone (GH) levels of LID-TRAMP mice were 3.5-fold elevated relative to L/L-TRAMP mice (P < 0.001), but IGFBP-2 levels were not different. Surprisingly, rates of survival, metastasis, and the ratio of genitourinary tissue weight to body weight were not significantly different between LID-TRAMP and L/L-TRAMP mice. There was also no difference in the pathologic stage of the prostate cancer between the two groups at 9 to 19 weeks of age. LID-TRAMP tumors displayed increased levels of GH receptors and increased Akt phosphorylation. These results are in striking contrast with the published model of the GH-deficient lit/lit-TRAMP, which has smaller tumors and improved survival, and indicate that the reduction in systemic IGF-I is not sufficient to inhibit prostate cancer tumor progression in the TRAMP model, which may require a reduction of GH levels as well.

Original languageEnglish (US)
Pages (from-to)3342-3349
Number of pages8
JournalCancer Research
Issue number9
StatePublished - May 1 2008


ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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