Expression analysis of MAC30 in human pancreatic cancer and tumors of the gastrointestinal tract
H. Kayed1, J. Kleeff1, J. Ding2, J. Hammer2, T. Giese3, H. Zentgraf4, M.W. Büchler1 and H. Friess1
1Department of General Surgery, University of Heidelberg, Heidelberg, Germany, 2Roche Genomic and Information Sciences, Hoffmann-La Roche Inc., Nutley, New Jersey, USA, 3Institute of Immunology, University of Heidelberg, Heidelberg, Germany and 4Department of Applied Tumor Virology, German Cancer Research Center, Heidelberg, Germany
Offprint requests to: Helmut Friess, M.D., Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110 69120 Heidelberg, Germany. e-mail: Helmut_Friess@med.uni-heidelberg.de
Summmary. Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-ß on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-ß down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies. Histol Histopathol 19, 1021-1031 (2004)
Key words: MAC30, Pancreatic cancer, Chronic pancreatitis, Gastric cancer, Colon Cancer
DOI: 10.14670/HH-19.1021