Bcl-XL protein levels determine apoptotic index in pancreatic carcinoma.

Abstract

OBJECTIVES:

The present study was designed to analyze the expression of the major antiapoptotic molecules Bcl-2, Bcl-XL and the proapoptotic Bax in pancreatic ductal carcinoma and their correlation to the extent of apoptosis.

METHODS:

Tissue samples were obtained from patients (age, 27-78 years) having surgery for pancreatic cancer. Normal pancreatic tissue away from the main tumor mass was also analyzed. The levels of Bcl-2, Bcl-XL, and Bax mRNA expression were analyzed by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The presence of corresponding proteins was determined by immunohistochemistry (IHC). The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay.

RESULTS:

A total of 25 cases were analyzed. The apoptotic index (percentage) ranged from 0.0% to 1.8%, with a median of 0.26. Semiquantitative RT-PCR revealed variable mRNA expression, with the Bcl-2/Bax ratio ranging from 0.2 to 1.5 and the Bcl-XL/Bax ratio ranging from 0.3 to 1.8. There was no correlation of mRNA levels with the apoptotic index. Immunohistochemical analysis showed positive Bcl-2, Bax, Bcl-XL expression in 20%, 72%, and 92% of cancer samples; however, their levels were variable. Spearman rank correlation coefficient test revealed a significant inverse association for the Bcl-XL IHC score and apoptotic index (P < 0.05). In contrast, Bcl-2, Bax protein levels did not show any association with the apoptotic index. However, as compared with the normal pancreas, Bcl-2, Bcl-XL, Bax were overexpressed in most of the pancreatic cancer samples (Mann-Whitney U test, P < 0.01).

CONCLUSION:

In pancreatic cancer, there is an upregulation of all the apoptotic regulatory molecules and the apoptotic index is chiefly determined by Bcl-XL protein levels.

• Authors: Jyotika Sharma, Radhika Srinivasan, Siddhartha Majumdar, Snober Mir, Bishan Dass Radotra, Jai Dev Wig
• Journal: Pancreas (Pancreas) Vol. 30 Issue 4 Pg. 337-42 (May 2005) ISSN: 1536-4828 [Electronic] United States
• PMID: 15841044 (Publication Type: Journal Article)

Chemical References

• BCL2L1 protein, human
• Biomarkers, Tumor
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger
• bcl-2-Associated X Protein
• bcl-X Protein

Topics

• Adult
• Aged
• Apoptosis
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma, Pancreatic Ductal (metabolism, pathology)
• Female
• Humans
• Immunohistochemistry
• In Situ Nick-End Labeling
• Male
• Middle Aged
• Pancreatic Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• RNA, Messenger (analysis)
• Reverse Transcriptase Polymerase Chain Reaction
• Up-Regulation
• bcl-2-Associated X Protein (genetics, metabolism)
• bcl-X Protein (genetics, metabolism)