Apoptosis--also called programmed cell death--plays an important role in
tissue homeostasis and in the elimination of abnormal cells, thereby preventing
malignant cell transformation. Bak is an apoptosis promoting gene which belongs
to the Bcl-2 gene family. Pancreatic cancer is a rapid growing malignancy with
poor prognosis. The reasons for its aggressive growth behavior are not known. In
the present study we analyzed the expression of Bak in human pancreatic cancer
to evaluate if apoptosis is activated or inhibited in this malignancy.
Patients: Pancreatic cancer tissues were obtained from 18 male and 8 female
patients (median age: 67 years; range: 32-78 years) undergoing resection for
pancreatic cancer (3 stage I, 12 stage II, 11 stage III). Normal pancreatic
tissue samples were obtained from 12 previously healthy organ donors through an
organ donor program (9 male, 3 female; median age: 26 years; range: 10-62
years).
Methods: Bak mRNA expression was analyzed by Northern blot analysis. The
exact site of Bak mRNA localization was determined by in sltu hybridization. The
results of the Northern blots were quantified by laser densitometry for
statistical analysis. The in situ hybridization slides were examined by two
independent pathologists.
Results: Bak mRNA expression was 2.5-fold increased in the pancreatic cancer
samples in comparison with normal pancreas (p<0.001). Elevated levels were
found in 58% (15/26) of pancreatic cancer tissues. If only samples with
increased Bak expression were used for statistical analysis the increase was
4.3-fold compared to normal controls (p<0.001). There was no correlation
between tumor-stage, patient survival and Bak expression. By in situ
hybridization, low to moderate levels of Bak mRNA expression were present in
ductal and islet cells in the normal pancreas. In the cancer tissues we also
found only low levels of Bak mRNA in the cancer cells themselves. In contrast,
in regions with chronic pancreatitis-like lesions surrounding the tumor mass
there was consistently high Bak mRNA expression in acinar and in inflammatory
cells.
Conclusion: Downregulation of Bak in pancreatic cancer cells, but not in the
cells within the regions of perifocal chronic pancreatitis, suggests that
apoptosis is not activated in pancreatic cancer. The absence of apoptosis
promoting gene products in pancreatic cancer might contribute to the aggressive
growth behavior and spread of this tumor.
