Antitumour activity of docetaxel (Taxotere) in hormone-dependent (HD) and 
hormone-independent (HID) prostate cancer PAC120 xenograft model was previously 
reported, and its level was associated with HER2 protein expression. In the 
present study, we evaluate the antitumour effects of docetaxel combined with 
trastuzumab (Herceptin), an anti-HER2 antibody. Although trastuzumab alone had 
no effect on tumour growth, it potentiated the antitumour activity of docetaxel 
in HD tumours and more strongly in HID variants. Using the HID28 variant, we 
show that docetaxel treatment of tumour-bearing mice induces an increased HER2 
mRNA expression of the tyrosine kinase receptor of 25-fold 24 h after docetaxel 
treatment, while HER2 protein and p-AKT decreased. This was followed by an 
increase of HER2 protein 3 days (two-fold) after docetaxel treatment and by a 
strong HER2 release in the serum of treated mice; expression of phospho-ERK, 
p27, BCL2 and HSP70 concomitantly increased. Similar molecular alterations were 
induced by docetaxel plus trastuzumab combination, except for that there was a 
transient and complete disappearance of AR and HSP90 proteins 24 h after 
treatment. We show that in addition to its known effects on tubulin and mitotic 
spindles, docetaxel induces complex signalisation pathway mechanisms in 
surviving cells, including HER2, which can be pharmacologically targeted. This 
study suggests that the docetaxel/trastuzumab combination may prove an effective 
therapeutic approach for HER2-expressing hormone-refractory prostate cancer.