RUNX3 expression in primary and metastatic pancreatic cancer.
OBJECTIVE
Runx transcription factors are important regulators of lineage specific gene expression, cell proliferation, and differentiation. Runx3 expression is lost in a high proportion of gastric cancers, suggesting a tumour suppressive role in this malignancy. This study investigates the expression and localisation of Runx3 in pancreatic tissues.


METHODS
Quantitative polymerase chain reaction was used to measure Runx3 mRNA. Immunohistochemistry was carried out to localise Runx3 in normal pancreatic tissues, and in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Basal and transforming growth factor beta1 (TGFbeta1) induced Runx3 expression was analysed in cultured pancreatic cancer cell lines.


RESULTS
Runx3 expression was low to absent in normal pancreatic tissues, but increased in a third of cancer tissues. Runx3 was present only in islets in normal pancreas, whereas in pancreatic cancers, Runx3 was detected in the cancer cells of seven of 24 samples analysed. In addition, it was expressed by lymphocytes in six of the 16 cases with lymphocyte infiltration. In pancreatic cancer cell lines, Runx3 mRNA was present in Colo-357 and T3M4 cells, but was low to absent in the other cell lines tested. TGFbeta1 repressed Runx3 mRNA expressed in Colo-357 cells, and had no effect on Runx3 expression in the other pancreatic cancer cell lines.


CONCLUSIONS
Runx3 expression is restricted to islets in the normal pancreas. In contrast, a considerable proportion of pancreatic tumours express Runx3, and its expression is localised in the tumour cells and in the infiltrating lymphocytes. Thus, Runx3 might play a role in the pathogenesis of PDAC.
Li
J
J
Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Kleeff
J
J
Guweidhi
A
A
Esposito
I
I
Berberat
P O
PO
Giese
T
T
Büchler
M W
MW
Friess
H
H
D000230:Adenocarcinoma / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western / Q000379:methods; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007515:Islets of Langerhans / Q000378:metabolism; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014407:Tumor Cells, Cultured
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C493729:Runx3 protein, human; C508960:TGFB1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1