title: Pathobiological implications of MUC16 expression in pancreatic cancer.
abstract: MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.
authors: Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors: Dhanya
authors: D
authors: Haridas
authors: Subhankar
authors: S
authors: Chakraborty
authors: Moorthy P
authors: MP
authors: Ponnusamy
authors: Imayavaramban
authors: I
authors: Lakshmanan
authors: Satyanarayana
authors: S
authors: Rachagani
authors: Eric
authors: E
authors: Cruz
authors: Sushil
authors: S
authors: Kumar
authors: Srustidhar
authors: S
authors: Das
authors: Subodh M
authors: SM
authors: Lele
authors: Judy M
authors: JM
authors: Anderson
authors: Uwe A
authors: UA
authors: Wittel
authors: Michael A
authors: MA
authors: Hollingsworth
authors: Surinder K
authors: SK
authors: Batra
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D015153:Blotting, Western; D018394:CA-125 Antigen / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D009362:Neoplasm Metastasis; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins