Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer

Kaiser, Ulrich; Schardt, Cordula; Brandscheidt, D.; Wollmer, Ellen; Havemann, K.

doi:10.1007/bf01215985

Cited by 53 publications

(23 citation statements)

References 15 publications

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“…In stratified analyses, the association was more predominant among patients receiving surgical operation, and there was a significant multiplicative interaction between risk genotypes and operation status. Both experimental and clinical studies have shown that the IGF-I receptor is overexpressed in lung and other carcinomas compared with normal tissues (34)(35)(36)(37), which might eliminate the downregulation effect of the variant genotypes of rs5742714 among patients without operation.…”

Section: Discussionmentioning

confidence: 99%

A 3′-Untranslated Region Polymorphism in IGF1 Predicts Survival of Non–Small Cell Lung Cancer in a Chinese Population

Zhang

Huang

et al. 2010

Clinical Cancer Research

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Purpose: Disruption of the balance of insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP3) has been implicated in the etiology and progression of lung and other cancers. Single nucleotide polymorphisms (SNP) in IGF1 and IGFBP3 have been reported to be associated with the expression of the IGF-I/IGFBP3 axis. Therefore, we hypothesized that SNPs in these two genes were associated with lung cancer survival.Experimental Design: We selected and genotyped 21 tagging and potentially functional SNPs in IGF1 and IGFBP3 by using Illumina Goldengate Genotyping Chip in a case cohort of 568 patients diagnosed with non-small cell lung cancer (NSCLC) in a Chinese population. Log-rank test and Cox proportional hazard models were used for the survival analyses.Results: We found that rs5742714C/G in the 3′-untranslated region of IGF1 was associated significantly with NSCLC survival after adjustment for demographic and clinicopathologic factors, showing an improved median survival time in patients carrying variant CG/GG genotypes [median survival time, 28.5 months for CG/GG and 23.0 for CC; crude hazard ratio (HR), 0.74; 95% confidence interval (95% CI), 0.57-0.95, and adjusted HR, 0.77; 95% CI, 0.60-0.99]. This protective effect was more predominant for patients receiving surgical operation (HR, 0.58; 95% CI, 0.40-0.85; P for heterogeneity test = 0.045), along with a significant multiplicative interaction between variant genotypes and operation status (P = 0.028).Conclusions: Our findings suggest that rs5742714 in IGF1 may be a genetic modifier for NSCLC prognosis in this Chinese population, especially among patients with surgical operation.

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Section: Discussionmentioning

confidence: 99%

A 3′-Untranslated Region Polymorphism in IGF1 Predicts Survival of Non–Small Cell Lung Cancer in a Chinese Population

Zhang

Huang

et al. 2010

Clinical Cancer Research

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“…Indeed, previous studies demonstrated that continuously high levels of IGF-I over the life span would lead to deleterious consequences and contribute to pathological changes associated with age through the effect on cell division and/or metabolism. In fact, due to the effect of IGF-I on cellular replication, this hormone has also been linked to the development of several diseases such as cancer (32,75). Thus it could be hypothesized that the decrease in plasma IGF-I observed in long-lived subjects might minimize the generalized mitogenic stimulus to tissues and then contribute to the reduction of agerelated pathologies.…”

Section: Humansmentioning

confidence: 99%

Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans

Barbieri¹,

Bonafè²,

Franceschi³

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

403

291

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Although the underlying mechanisms of longevity are not fully understood, it is known that mutation in genes that share similarities with those in humans involved in the insulin/insulin-like growth factor I (IGF-I) signal response pathway can significantly extend life span in diverse species, including yeast, worms, fruit flies, and rodents. Intriguingly, the long-lived mutants, ranging from yeast to mice, share some important phenotypic characteristics, including reduced insulin signaling, enhanced sensitivity to insulin, and reduced IGF-I plasma levels. Such genetic homologies and phenotypic similarities between insulin/IGF-I pathway mutants raise the possibility that the fundamental mechanism of aging may be evolutionarily conserved from yeast to mammals. Very recent findings also provide novel and intriguing evidence for the involvement of insulin and IGF-I in the control of aging and longevity in humans. In this study, we focus on how the insulin/IGF-I pathway controls yeast, nematode, fruit fly, and rodent life spans and how it is related to the aging process in humans to outline the prospect of a unifying mechanism in the genetics of longevity.

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“…In a transgenic carcinogenesis model involving simian virus 40 T antigen targeted to the ␤-islet cells, activation of the IGF-IR by IGF-II is a critical determinant of carcinogenic progression (8). Elevated levels of IGF-IR have been detected in human tumors of lung (22,32), breast (11,15,36), and colon (18,37), and this is often associated with increased levels of circulating IGF-I and/or IGF-II (4,29). For many such tumors, IGF-I acts as a mitogen in vitro (16,33), suggesting the involvement of IGF-IR autocrine or paracrine signaling loops in tumors in vivo (25,48).…”

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confidence: 99%

Identification of Domains of the Insulin-Like Growth Factor I Receptor That Are Required for Protection from Apoptosis

O’Connor¹,

Kauffmann‐Zeh²,

Liu³

et al. 1997

Molecular and Cellular Biology

239

173

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Using a series of insulin-like growth factor I (IGF-I) receptor mutants, we have attempted to define domains required for transmitting the antiapoptotic signal from the receptor and to compare these domains with those required for mitogenesis or transformation. In FL5.12 cells transfected with wild-type IGF-I receptors, IGF-I affords protection from interleukin 3 withdrawal but is not mitogenic. An IGF-I receptor lacking a functional ATP binding site provided no protection from apoptosis. However, receptors mutated at tyrosine residue 950 or in the tyrosine cluster (1131, 1135, and 1136) within the kinase domain remained capable of suppressing apoptosis, although such mutations are known to inactivate transforming and mitogenic functions. In the C terminus of the IGF-I receptor, two mutations, one at tyrosine 1251 and one which replaced residues histidine 1293 and lysine 1294, abolished the antiapoptotic function, whereas mutation of the four serines at 1280 to 1283 did not. Interestingly, receptors truncated at the C terminus had enhanced antiapoptotic function. In Rat-1/ c-MycER fibroblasts, the Y950F mutant and the tyrosine cluster mutant could still provide protection from c-Myc-induced apoptosis, whereas mutant Y1250/1251F could not. These studies demonstrate that the domains of the IGF-I receptor required for its antiapoptotic function are distinct from those required for its proliferation or transformation functions and suggest that domains of the receptor required for inhibition of apoptosis are necessary but not sufficient for transformation.

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Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer

Cited by 53 publications

References 15 publications

A 3′-Untranslated Region Polymorphism in IGF1 Predicts Survival of Non–Small Cell Lung Cancer in a Chinese Population

A 3′-Untranslated Region Polymorphism in IGF1 Predicts Survival of Non–Small Cell Lung Cancer in a Chinese Population

Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans

Identification of Domains of the Insulin-Like Growth Factor I Receptor That Are Required for Protection from Apoptosis

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