Molecular pattern of ductal pancreatic cancer.
Our understanding of the molecular pathology underlying the development and progression of ductal pancreatic cancer has been revolutionised during the last 5 years due to the spectacular development of novel molecular biological techniques. In the present article, we describe key molecular alterations of sporadic and inherited ductal pancreatic cancer. Overexpression of growth factors and growth factor receptors are present in a significant proportion of this tumour type. Mutation of the K-ras oncogene, and disruption of p53 or p16 tumour suppressor gene abrogates the control of the cyclin-dependent kinases (cdk) and retinoblastoma (Rb) gene pathway, causing continuous growth of the pancreatic tumour. Inactivation of the SMAD4 tumour suppressor gene leads to loss of the inhibitory influence of the transforming growth factor beta signalling pathway. Lost or decreased expression of retinoid receptors and failure of telomerase activity may play a role in pancreatic carcinogenesis. Tumour-associated proteinases, matrix metalloproteinases and plasminogen activators are reported to be involved in pancreatic cancer invasion and metastasis. Furthermore, the cytogenetic changes in this cancer are summarised. This molecular pattern distinguishes pancreatic cancer from other epithelial tumours and represents a promising basis for the development of diagnostic and other clinical applications.
Sirivatanauksorn
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Molecular Pathology Laboratory, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Sirivatanauksorn
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Y
Lemoine
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NR
D000230:Adenocarcinoma / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D010183:Pancreatic Ducts; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*
D014408:Biomarkers, Tumor; D006133:Growth Substances; D017978:Receptors, Growth Factor; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)