Local expression of insulin-like growth factor-I affects angiogenesis in colorectal cancer.
Insulin-like growth factor-I (IGF-I) has potent mitogenic and anti-apoptotic effects that give it a critical role in the regulation of rapidly renewing epithelial cell populations such as those found in the colon. Recent evidence has implicated circulating IGF-I levels as an important determinant of colorectal cancer risk, but the role, if any, of its autocrine/paracrine expression remains unexplored. Therefore, we investigated the local expression of IGF-I and IGF-I type I receptor (IGF-IR) in 50 paired normal colon and carcinoma samples. IGF-IR mRNA was present in all samples, whereas IGF-I mRNA was detected in only 30 normal (60%) and 27 tumour (54%) biopsies. Samples that did not express IGF-I mRNA had no IGF-I peptide detectable by immunocytochemistry. The absence of local IGF-1 expression was associated with significantly reduced mRNA levels specifying the proliferating cell nuclear antigen and c-myc, as well as Cox-2, and vascular endothelial growth factor - gene products that regulate angiogenesis. The biological relevance of this finding is suggested by the significant association between local IGF-I mRNA levels and microvessel density in the colorectal cancers.
Bustin
Stephen A
SA
Academic Department of Surgery, Barts and the London Queen Mary's School of Medicine and Dentistry, London, UK. s.a.bustin@mds.qmw.ac.uk
Dorudi
Sina
S
Phillips
Simon M
SM
Feakins
Roger M
RM
Jenkins
Paul J
PJ
D001706:Biopsy; D002277:Carcinoma / Q000098:blood supply* / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1