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Genetic Reduction of Insulin-like Growth Factor-1 Mimics the Anticancer Effects of Calorie Restriction on Cyclooxygenase-2–Driven Pancreatic Neoplasia

Overview of attention for article published in Cancer Prevention Research, July 2011
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Title
Genetic Reduction of Insulin-like Growth Factor-1 Mimics the Anticancer Effects of Calorie Restriction on Cyclooxygenase-2–Driven Pancreatic Neoplasia
Published in
Cancer Prevention Research, July 2011
DOI 10.1158/1940-6207.capr-11-0027
Pubmed ID
Authors

Laura M. Lashinger, Lauren M. Malone, Mark J. McArthur, Jason A. Goldberg, Elizabeth A. Daniels, Amy Pavone, Jennifer K. Colby, Nicole C. Smith, Susan N. Perkins, Susan M. Fischer, Stephen D. Hursting

Abstract

Risk of pancreatic cancer, the fourth deadliest cancer in the United States, is increased by obesity. Calorie restriction (CR) prevents obesity, suppresses carcinogenesis in many models, and reduces serum levels of IGF-1. In the present study, we examined the impact of CR on a model of inflammation-associated pancreatitis and pancreatic dysplasia, with a focus on the mechanistic contribution of systemic IGF-1. Administration of a 30% CR diet for 14 weeks decreased serum IGF-1 levels and hindered pancreatic ductal lesion formation and dysplastic severity, relative to a higher calorie control diet, in transgenic mice overexpressing COX-2 [bovine keratin-5 promoter (BK5.COX-2)]. These findings in CR mice correlated with reductions in Ki-67-positive cells, vascular luminal size, VEGF expression, and phosphorylation and total expression of downstream mediators of the IGF-1 pathway. Cell lines derived from BK5.COX-2 ductal lesions (JC101 cells) formed pancreatic tumors in wild-type FVB mice that were significantly reduced in size by a 14-week CR regimen, relative to the control diet. To further understand the impact of circulating levels of IGF-1 on tumor growth in this model, we orthotopically injected JC101 cells into liver-specific IGF-1-deficient (LID) mice. The approximate 65% reduction of serum IGF-1 levels in LID mice resulted in significantly decreased burden of JC101 tumors, despite modestly elevated levels of circulating insulin and leptin. These data show that CR prevents development of dysplasia and growth of pancreatic cancer through alterations in IGF-1, suggesting that modulation of this pathway with dietary and/or pharmacologic interventions is a promising pancreatic cancer prevention strategy.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 40 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 5%
Unknown 38 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 18%
Student > Postgraduate 6 15%
Student > Master 6 15%
Researcher 5 13%
Student > Bachelor 5 13%
Other 9 23%
Unknown 2 5%
Readers by discipline Count As %
Medicine and Dentistry 14 35%
Agricultural and Biological Sciences 13 33%
Biochemistry, Genetics and Molecular Biology 7 18%
Nursing and Health Professions 2 5%
Psychology 1 3%
Other 1 3%
Unknown 2 5%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 October 2022.
All research outputs
#20,450,513
of 23,006,268 outputs
Outputs from Cancer Prevention Research
#1,266
of 1,365 outputs
Outputs of similar age
#108,116
of 116,874 outputs
Outputs of similar age from Cancer Prevention Research
#29
of 33 outputs
Altmetric has tracked 23,006,268 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,365 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.2. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 116,874 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 33 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.