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.
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