Korean J Intern Med.  2013 Sep;28(5):573-578. 10.3904/kjim.2013.28.5.573.

Expression of procaspase 3 and activated caspase 3 and its relevance in hormone-responsive gallbladder carcinoma chemotherapy

• Maurya SK
• Tewari M
• Sharma B
• Shukla HS

• KMID: 1780105
• DOI: http://doi.org/10.3904/kjim.2013.28.5.573

Abstract

BACKGROUND/AIMS
The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC.
METHODS
We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies.
RESULTS
ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC.
CONCLUSIONS
The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis.

Keyword

Gallbladder neoplasms; Antiapoptotic molecules; Apoptosis; Signal transduction; Up-regulation

MeSH Terms

Antineoplastic Agents, Hormonal/therapeutic use
*Apoptosis/drug effects
Blotting, Western
Carcinoma/drug therapy/*enzymology/pathology
Caspase 3/*analysis
Drug Resistance, Neoplasm
Enzyme Activation
Gallbladder Neoplasms/drug therapy/*enzymology/pathology
Humans
Neoplasms, Hormone-Dependent/drug therapy/*enzymology/pathology
Receptor, erbB-2/analysis
Receptors, Androgen/analysis
Receptors, Estrogen/analysis
Tumor Markers, Biological/*analysis
Antineoplastic Agents, Hormonal
Caspase 3
Receptors, Androgen
Receptors, Estrogen
Tumor Markers, Biological
Receptor, erbB-2