Gene expression profiles in primary pancreatic tumors and metastatic lesions of Ela-c-myc transgenic mice.
BACKGROUND
Pancreatic carcinoma usually is a fatal disease with no cure, mainly due to its invasion and metastasis prior to diagnosis. We analyzed the gene expression profiles of paired primary pancreatic tumors and metastatic lesions from Ela-c-myc transgenic mice in order to identify genes that may be involved in the pancreatic cancer progression. Differentially expressed selected genes were verified by semi-quantitative and quantitative RT-PCR. To further evaluate the relevance of some of the selected differentially expressed genes, we investigated their expression pattern in human pancreatic cancer cell lines with high and low metastatic potentials.


RESULTS
Data indicate that genes involved in posttranscriptional regulation were a major functional category of upregulated genes in both primary pancreatic tumors (PT) and liver metastatic lesions (LM) compared to normal pancreas (NP). In particular, differential expression for splicing factors, RNA binding/pre-mRNA processing factors and spliceosome related genes were observed, indicating that RNA processing and editing related events may play critical roles in pancreatic tumor development and progression. High expression of insulin growth factor binding protein-1 (Igfbp1) and Serine proteinase inhibitor A1 (Serpina1), and low levels or absence of Wt1 gene expression were exclusive to liver metastatic lesion samples.


CONCLUSIONS
We identified Igfbp1, Serpina1 and Wt1 genes that are likely to be clinically useful biomarkers for prognostic or therapeutic purposes in metastatic pancreatic cancer, particularly in pancreatic cancer where c-Myc is overexpressed.
Thakur
Archana
A
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, 110 E, Warren Ave,, Detroit, Michigan 48201, USA. athakur@med.wayne.edu
Bollig
Aliccia
A
Wu
Jiusheng
J
Liao
Dezhong J
DJ
D000818:Animals; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015870:Gene Expression; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D018970:Insulin-Like Growth Factor Binding Protein 1; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D025721:WT1 Proteins