Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors

Yiping Wu, Karen Cui, Keiko Miyoshi, Lothar Hennighausen, Jeffrey E. Green, Jennifer Setser, Derek LeRoith, Shoshana Yakar

Research output: Contribution to journalArticle

Abstract

Insulin-like growth factors (IGFs) play a crucial role in regulating cell proliferation and differentiation. The aim of this study was to examine the potential relationship between serum IGF-I levels and breast cancer risk. To do this, we studied liver-specific IGF-I gene-deleted (LID) mice, in which circulating IGF-I levels are 25% of that in control mice. Mammary tumors were induced in two ways: (a) by exposing mice to the carcinogen 7,12-dimethybenz (a)anthracene; and (b) by crossing LID mice with C3(1)/SV40 large T-antigen transgenic mice. In both models, LID mice exhibited a delayed latency period of mammary tumor development. In the 7,12-dimethybenz (a)anthracene-induced mammary tumor model, the incidence of palpable mammary tumors was significantly lower in LID mice (26% versus 56% in controls), and the onset of the tumors was delayed (74 ± 1.2 days in LID mice versus 59.5 ± 1.1 days in controls). Histological analysis showed extensive squamous metaplasia in late-stage mammary tumors of control mice, whereas late-stage tumors from LID mice exhibited extensive hyperplasia, but little metaplasia. In control mice, the onset of C3(1)/SV40-large T-antigen-induced mammary tumors occurred at 21.6 ± 1.8 weeks of age, whereas in LID mice the average age of onset was 30.2 ± 1.7 weeks. In addition, 60% of the mice in the control group developed two or more mammary tumors per mouse, whereas in the LID mice only 30% developed more than one mammary tumor per mouse. Our data demonstrate that circulating IGF-I levels play a significant role as a risk factor in the onset and development of mammary tumors in two well-established animal models of breast cancer.

Original languageEnglish (US)
Pages (from-to)4384-4388
Number of pages5
JournalCancer Research
Volume63
Issue number15
StatePublished - Aug 1 2003

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Insulin-Like Growth Factor I
Breast Neoplasms
Liver
Genes
Polyomavirus Transforming Antigens
Viral Tumor Antigens
Metaplasia
Somatomedins
Age of Onset
Carcinogens
Transgenic Mice
Hyperplasia
Cell Differentiation
Neoplasms
Animal Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wu, Y., Cui, K., Miyoshi, K., Hennighausen, L., Green, J. E., Setser, J., ... Yakar, S. (2003). Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Research, 63(15), 4384-4388.

Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. / Wu, Yiping; Cui, Karen; Miyoshi, Keiko; Hennighausen, Lothar; Green, Jeffrey E.; Setser, Jennifer; LeRoith, Derek; Yakar, Shoshana.

In: Cancer Research, Vol. 63, No. 15, 01.08.2003, p. 4384-4388.

Research output: Contribution to journalArticle

Wu, Y, Cui, K, Miyoshi, K, Hennighausen, L, Green, JE, Setser, J, LeRoith, D & Yakar, S 2003, 'Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors', Cancer Research, vol. 63, no. 15, pp. 4384-4388.
Wu Y, Cui K, Miyoshi K, Hennighausen L, Green JE, Setser J et al. Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Research. 2003 Aug 1;63(15):4384-4388.
Wu, Yiping ; Cui, Karen ; Miyoshi, Keiko ; Hennighausen, Lothar ; Green, Jeffrey E. ; Setser, Jennifer ; LeRoith, Derek ; Yakar, Shoshana. / Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. In: Cancer Research. 2003 ; Vol. 63, No. 15. pp. 4384-4388.
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abstract = "Insulin-like growth factors (IGFs) play a crucial role in regulating cell proliferation and differentiation. The aim of this study was to examine the potential relationship between serum IGF-I levels and breast cancer risk. To do this, we studied liver-specific IGF-I gene-deleted (LID) mice, in which circulating IGF-I levels are 25{\%} of that in control mice. Mammary tumors were induced in two ways: (a) by exposing mice to the carcinogen 7,12-dimethybenz (a)anthracene; and (b) by crossing LID mice with C3(1)/SV40 large T-antigen transgenic mice. In both models, LID mice exhibited a delayed latency period of mammary tumor development. In the 7,12-dimethybenz (a)anthracene-induced mammary tumor model, the incidence of palpable mammary tumors was significantly lower in LID mice (26{\%} versus 56{\%} in controls), and the onset of the tumors was delayed (74 ± 1.2 days in LID mice versus 59.5 ± 1.1 days in controls). Histological analysis showed extensive squamous metaplasia in late-stage mammary tumors of control mice, whereas late-stage tumors from LID mice exhibited extensive hyperplasia, but little metaplasia. In control mice, the onset of C3(1)/SV40-large T-antigen-induced mammary tumors occurred at 21.6 ± 1.8 weeks of age, whereas in LID mice the average age of onset was 30.2 ± 1.7 weeks. In addition, 60{\%} of the mice in the control group developed two or more mammary tumors per mouse, whereas in the LID mice only 30{\%} developed more than one mammary tumor per mouse. Our data demonstrate that circulating IGF-I levels play a significant role as a risk factor in the onset and development of mammary tumors in two well-established animal models of breast cancer.",
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