Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice

C. E. Rogler, D. Yang, L. Rossetti, J. Donohoe, E. Alt, C. J. Chang, Ronald (Ron) Rosenfeld, K. Neely, R. Hintz

Research output: Contribution to journalArticle

234 Citations (Scopus)

Abstract

The physiological role of insulin-like growth factor (IGF) II (IGF-II) in adult humans is poorly understood. Rather high levels of IGF-II persist in adult human serum, whereas, in rodents, IGF-II levels are very low. To investigate the physiological and carcinogenic effects of persistently elevated IGF-II in adults, we have produced two lines of transgenic mice in which high levels of IGF-II (20- or 30-fold increase above normal) are persistently maintained in the blood. The transgene is driven by the major urinary protein promoter, and it is highly expressed in the liver and perputial glands in both lines. The adult transgenic mice are smaller than controls, and their body composition is altered. Their lean body mass is reduced by 5-8%, whereas fat mass is reduced between 44 and 77%. The mice expressing the highest level of IGF-II (30x) develop hypoglycemia and hypoinsulinemia and IGF-I levels are normal. Mice in the lower expression line (20-fold elevated IGF-II) develop hypoglycemia progressively over their lifetime. Mice from both lines also develop a diverse spectrum of tumors at a higher frequency than controls after 18 months of age, and the most frequent types of tumors are hepatocellular carcinomas and lymphomas. Squamous cell carcinoma, sarcoma, and thyroid carcinomas also occurred in our test group. The long latent period before tumors arise and the wide spectrum of tumor types suggest that IGF-II may function primarily as a tumor progression factor in mice via autocrine and endocrine mechanisms of action.

Original languageEnglish (US)
Pages (from-to)13779-13784
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number19
StatePublished - 1994
Externally publishedYes

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Insulin-Like Growth Factor II
Body Composition
Transgenic Mice
Tumors
Chemical analysis
Neoplasms
Hypoglycemia
Transgenes
Insulin-Like Growth Factor I
Thyroid Neoplasms
Sarcoma
Liver
Hepatocellular Carcinoma
Squamous Cell Carcinoma
Rodentia
Lymphoma
Blood
Fats
Serum

ASJC Scopus subject areas

  • Biochemistry

Cite this

Rogler, C. E., Yang, D., Rossetti, L., Donohoe, J., Alt, E., Chang, C. J., ... Hintz, R. (1994). Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. Journal of Biological Chemistry, 269(19), 13779-13784.

Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. / Rogler, C. E.; Yang, D.; Rossetti, L.; Donohoe, J.; Alt, E.; Chang, C. J.; Rosenfeld, Ronald (Ron); Neely, K.; Hintz, R.

In: Journal of Biological Chemistry, Vol. 269, No. 19, 1994, p. 13779-13784.

Research output: Contribution to journalArticle

Rogler, CE, Yang, D, Rossetti, L, Donohoe, J, Alt, E, Chang, CJ, Rosenfeld, RR, Neely, K & Hintz, R 1994, 'Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice', Journal of Biological Chemistry, vol. 269, no. 19, pp. 13779-13784.
Rogler, C. E. ; Yang, D. ; Rossetti, L. ; Donohoe, J. ; Alt, E. ; Chang, C. J. ; Rosenfeld, Ronald (Ron) ; Neely, K. ; Hintz, R. / Altered body composition and increased frequency of diverse malignancies in insulin-like growth factor-II transgenic mice. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 19. pp. 13779-13784.
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