Role of the insulin-like growth factor family in cancer development and progression

Herbert Yu, Thomas E. Rohan

Research output: Contribution to journalArticle

1111 Citations (Scopus)

Abstract

The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth. The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-I and low levels of IGFBP-3 are associated with increased risk of several common cancers, including those of the prostate, breast, colorectum, and lung. Evidence further suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth. Further investigation of the role of IGFs in linking high energy intake, increased cell proliferation, suppression of apoptosis, and increased cancer risk may provide new insights into the etiology of cancer and lead to new strategies for cancer prevention.

Original languageEnglish (US)
Pages (from-to)1472-1489
Number of pages18
JournalJournal of the National Cancer Institute
Volume92
Issue number18
StatePublished - Sep 20 2000

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Somatomedins
Neoplasms
Insulin-Like Growth Factor Binding Proteins
Insulin-Like Growth Factor I
Cell Proliferation
Apoptosis
Oncogenic Viruses
IGF Type 1 Receptor
Insulin-Like Growth Factor Binding Protein 3
Oncogene Proteins
Growth
Energy Intake
Mitogens
Life Style
Epidemiologic Studies
Prostate
Cell Differentiation
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Breast

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Role of the insulin-like growth factor family in cancer development and progression. / Yu, Herbert; Rohan, Thomas E.

In: Journal of the National Cancer Institute, Vol. 92, No. 18, 20.09.2000, p. 1472-1489.

Research output: Contribution to journalArticle

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