Bak expression and cell death occur in peritumorous tissue but not in pancreatic cancer cells

Bak is a pro-apoptotic member of the Bcl-2 family whose genes are involved in regulation of programmed cell death. Using in situ hybridization, immuno histochemistry, and Northern blot analysis, we studied the expression of Ba k in specimens from 12 normal pancreata and 26 primary pancreatic cancers, and correlated the findings with the clinical and histopathologic data of t he patients. By comparison with normal pancreas, Northern blot analysis dem onstrated a 2.5-fold increase of Bak messenger RNA expression in the tumor samples (P <0.001). Elected levels were found in 15 of the 26 pancreatic ca ncer tissue specimens. in these samples Bak expression was increased 4.3 fo ld (P <0.001). No association was detected between Bak expression and tumor stage. In situ hybridization and immunohistochemistry revealed that the tu mor cells themselves and the stroma cells expressed only low levels of Bak. In contrast, in regions adjacent to the tumor, which showed chronic inflam mation, there was always high expression in the acinar and inflammatory cel ls, explaining the increased Bak levels found in the tumor samples by means of Northern blot analysis. In the normal pancreas the expression of Bak wa s generally moderate in the acinar cells and low in the ductal and islet ce lls. In situ analysis using the terminal deoxynucleotidyl transferase metho d further showed that there was extensive cell death in the peritumorous ar eas with chronic inflammation. Taken together, these results suggest that i n pancreatic cancer Ball expression and programmed cell death are present i n cells that are localized in regions of chronic inflammation surrounding t he pancreatic cancer cells but not in the tumor cells themselves, a situati on that may facilitate tumor growth and spread.