2011
DOI: 10.1016/j.ajpath.2011.08.026
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Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced after Benign Prostate Epithelial Differentiation and TGF-β Treatment

Abstract: The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tis… Show more

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Cited by 24 publications
(16 citation statements)
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References 51 publications
(56 reference statements)
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“…This observation was discordant from our initial cross-study analysis of independent gene expression datasets identifying downregulated IGF1 as part of an 11-gene signature of PCa aggressiveness (Additional file 12: Table S11). One recent study shows evidence for decreased IGF1 mRNA in local PCa compared to benign prostate, although IGF1 may still be involved in subsequent tumor progression as this study did not evaluate advanced or metastatic disease [48]. In contrast, our immunohistochemical findings correlate with most literature on the role of increased IGF1 in cancer progression.…”
Section: Discussionsupporting
confidence: 77%
“…This observation was discordant from our initial cross-study analysis of independent gene expression datasets identifying downregulated IGF1 as part of an 11-gene signature of PCa aggressiveness (Additional file 12: Table S11). One recent study shows evidence for decreased IGF1 mRNA in local PCa compared to benign prostate, although IGF1 may still be involved in subsequent tumor progression as this study did not evaluate advanced or metastatic disease [48]. In contrast, our immunohistochemical findings correlate with most literature on the role of increased IGF1 in cancer progression.…”
Section: Discussionsupporting
confidence: 77%
“…Although this conclusion is unexpected because IGF-1R signaling is thought to promote tumor proliferation in prostate and other cancers (41), this receptor can also promote differentiation (42, 43) and this function may need to be impeded by VEGF/NRP2 signaling for the genesis of high-grade, aggressive cancer. This possibility is supported by the report that abrogation of functional IGF-IR expression actually promoted earlier emergence of more aggressive, less-differentiated carcinomas in a p53-compromised model of prostate cancer (44).…”
Section: Discussionmentioning
confidence: 99%
“…cDNA synthesis was performed using iScript select cDNA synthesis kit (Bio-Rad Laboratories). qPCR was performed on an ABI Prism 7500 fast real-time PCR System (Applied Biosystems, Life Technologies) as previously described [63,64]. Primer and TaqMan probes for IGF1R, INSR, INSRA, INSRB and the endogenous control HPRT1 were designed according to sequences from the Nucleotide Sequence Database NCBI using ABI Prism Primer Express Software 2.0.0 (Applied Biosystems, Life Technologies): IGF1R (forward primer, 5'-CCTCCAACTTCGTCTTTGCAA-3'; reverse primer, 5'-CAGGTCACTGGCCCAGGA-3'; probe, 5'-TGCCCGCAGAAGGAGCAGATGACA-3'); INSR (forward primer, 5´-CAAGTGCATCCCTGAGTGTCC-3´; reverse primer, 5´-CGAGTCGATGGTCTTCTCGC-3´; probe, 5'-GATGAATTCCAGCAACTTGCTGTGACC-3'); INSRA (forward primer, 5´- tggttttcgtccccaggcc-3´; reverse primer, 5´- ccaccgtcacattcccaac-3´; probe, 5'-tctcggaaacgcaggtcccttggcga-3'); INSRB (forward primer, 5´-gtgccgaggaccctaggcc-3´, reverse primer, 5´-ccaccgtcacattcccaac-3´, probe, 5'-tctcggaaacgcaggtcccttggcga-3') and HPRT1 (forward primer, 5´-gctttccttggtcaggcagta-3´; reverse primer; 5´- gtctggcttatatccaacacttcgt-3´; probe, 5'-gtctggcttatatccaacacttcgt-3').…”
Section: Methodsmentioning
confidence: 99%
“…All TaqMan probes were labeled with 6-Fam reporter dye and Tamra quencher dye. TaqMan gene expression assays were performed as previously described [66,67]. …”
Section: Methodsmentioning
confidence: 99%