The role of the insulin-like growth factor receptor, the insulin receptor substrate and PTEN in human prostate cancer progression

Hellawell, Giles; Turner, Gareth D. H.; Davies, David Roland; Brewster, Simon; Macaulay, Val

doi:10.1016/s1569-9056(02)80120-8

Cited by 31 publications

(9 citation statements)

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“…The IGF-IR has been linked with metastatic potential (Long et al, 1995(Long et al, , 1998Dunn et al, 1998;Brodt et al, 2000Brodt et al, , 2001Hellawell et al, 2002;Lopez and Hanahan, 2002). Our study has identified potential new mediators of this activity.…”

Section: Discussionmentioning

confidence: 99%

“…All of these IGF-IR functions are critical for normal development and homeostasis, but the IGF-IR and its ligands also contribute to cancer by promoting tumour growth, invasion, and metastasis. In prostate cancers, IGF-IR expression is stronger in both primary and metastatic prostate cancer cells than in normal tissue (Hellawell et al, 2002). In a mouse model of pancreatic cancer employing targeted expression of SV40 large T antigen enforced expression of the IGF-IR resulted in development of highly invasive and metastatic tumours (Lopez and Hanahan, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Gene expression profiles in cells transformed by overexpression of the IGF-I receptor

et al. 2005

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To identify genes associated with insulin-like growth factor-I receptor (IGF-IR)-mediated cellular transformation, we isolated genes that are differentially expressed in R À cells (derived from the IGF-IR knockout mouse) and R þ cells (R À cells that overexpress the IGF-IR). From these, 45 genes of known function were expressed at higher levels in R þ cells and 22 were expressed at higher levels in R À cells. Differential expression was confirmed by Northern blot analysis of R þ and R À cells. Genes expressed more abundantly in R þ cells are associated with (1) tumour growth and metastasis including, bigH3, mts1, igfbp5 protease, and mystique; (2) cell division, including cyclin A1 and cdk1; (3) signal transduction, including pkcdbp and lmw-ptp; and (4) metabolism including ATPase H þ transporter and ferritin. In MCF-7 cells IGF-I induced expression of two genes, lasp-1 and mystique, which could contribute to metastasis. Lasp-1 expression required activity of the PI3-kinase signalling pathway. Mystique was highly expressed in metastatic but not in androgen-dependent prostate cancer cell lines and Mystique overexpression in MCF-7 cells promoted cell migration and invasion. We conclude that genes identified in this screen may mediate IGF-IR function in cancer progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gene expression profiles in cells transformed by overexpression of the IGF-I receptor

et al. 2005

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“…Motility of many cancer cell types is stimulated by growth factors such as insulinlike growth factor I (IGF-I) (Sahai and Marshall, 2002). Increased levels of the type I IGF receptor (IGF-IR) are found in the majority of primary and metastatic CaP patient tumors (Hellawell et al, 2002). Functional IGF-IR is expressed on PC-3 cells (Iwamura et al, 1993;Kimura et al, 1996), and bone is a rich source of IGF-I, which is thought to act as a chemoattractant in CaP bone metastasis (Cooper and Pienta, 2000).…”

Section: Introductionmentioning

confidence: 99%

RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility

et al. 2005

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“…Both genetic and lifestyle factors influence IGF-I levels (Harrela et al, 1996). Epidemiologic data showing variation of prostate cancer risk according to IGF-I levels are biologically plausible given that normal prostate epithelial cells (Cohen et al, 1991) as well as prostate cancer cells (Culig et al, 1994;Pollak et al, 1999;Hellawell et al, 2002) are IGF-I responsive. While specific genetic loci responsible for interindividual variation in circulating IGF-I levels in normal men have not been identified, candidate genes include those involved in the growth hormone (GH)-IGF-I axis such as the hypothalamic factors GH releasing hormone (GHRH) and somatostatin and their receptors.…”

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confidence: 99%

A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model

et al. 2005

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Circulating insulin-like growth factor-I (IGF-I) levels have been shown to be related to risk of prostate cancer in epidemiologic studies. While specific genetic loci responsible for interindividual variation in circulating IGF-I levels in normal men have not been identified, candidate genes include those involved in the growth hormone (GH)-IGF-I axis such as the hypothalamic factors GH releasing hormone (GHRH) and somatostatin and their receptors. To investigate the role of the GH-IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we generated mice genetically predisposed to prostate cancer (the TRAMP model) to be homozygous for lit, a mutation that inactivates the GHRH receptor (GHRH-R) and reduces circulating levels of GH and IGF-I. The lit mutation significantly reduced the percentage of the prostate gland showing neoplastic changes at 35 weeks of age (P ¼ 0.0005) and was also associated with improved survival (Po0.01). These data provide an example of a germ line mutation that reduces risk in an experimental prostate carcinogenesis model. The results suggest that prostate carcinogenesis and progression may be influenced by germ line variation of genes encoding signalling molecules in the GH-IGF-I axis.

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The role of the insulin-like growth factor receptor, the insulin receptor substrate and PTEN in human prostate cancer progression

Cited by 31 publications

References 0 publications

Gene expression profiles in cells transformed by overexpression of the IGF-I receptor

Gene expression profiles in cells transformed by overexpression of the IGF-I receptor

RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility

A germ line mutation that delays prostate cancer progression and prolongs survival in a murine prostate cancer model

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