Differential expression patterns of the insulin-like growth factor 2 gene in human colorectal cancer.
Tumour development and metastasis are associated with altered gene expression profiles. The aim of this study was to identify the transcriptional differences in normal, tumour and metastatic tissue. We used oligonucleotide arrays to identify differential expression patterns of insulin-like growth factor 2 (IGF 2) between 139 primary colorectal tumour specimens and 42 tumour-adjacent mucosa specimens from colorectal cancer (CRC) patients. The expression levels of the IGF 2 gene were significantly increased in primary tumours compared with adjacent mucosae. This was concordant with our real-time RT-PCR quantification of 48 matched tumour mucosa samples. IGF 2 expression levels were also measured by RT-PCR quantitative analysis in 18 liver metastases and 10 normal tissues from patients without cancer. The mRNA levels were significantly under-expressed in liver metastases compared with either colorectal tumours or adjacent normal mucosae. The non- malignant normal tissue expressed significantly lower IGF 2 levels than adjacent normal tissue, and this was not due to a field effect originating from the tumour. In addition, our microarray data demonstrated that IGF 2 expression was down-regulated in sporadic microsatellite instability (MSI-H) CRC and parallels under-expression of hMLH1 and IGF 2 receptor genes in these patients. We conclude that IGF 2 plays an important role in CRC development. Also, individuals with loss of genomic imprinting (LOI) causing over-expression of IGF 2 may be at greater risk of developing CRC. However, this LOI may be reversed in MSI-H patients.
Li
Shu-Rui
SR
Centre for Academic Surgery, Institute of Cell and Molecular Science, Barts and the London, Queen Mary's School of Medicine and Dentistry, London, UK. s.r.li@qmul.ac.uk
Ng
Chung Fai Jeremy
CF
Banerjea
Ayan
A
Ahmed
Shafi
S
Hands
Rebecca
R
Powar
Michael
M
Ogunkolade
William
W
Dorudi
Sina
S
Bustin
Stephen A
SA
D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D015854:Up-Regulation
D004273:DNA, Neoplasm; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II