Title : Enhanced sensitization to taxol-induced apoptosis by herceptin pretreatment in ErbB2-overexpressing breast cancer cells.

Pub. Date : 2002 Oct 15

PMID : 12384528






4 Functional Relationships(s)
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1 Herceptin treatment down-regulated ErbB2, reduced the inhibitory phosphorylation of Cdc2 on Tyr-15, and down-regulated the expression of p21(Cip1), a Cdc2 inhibitor. Tyrosine cyclin dependent kinase 1 Homo sapiens
2 Herceptin plus Taxol treatment led to higher levels of p34(Cdc2) kinase activity and apoptosis in ErbB2-overexpressing breast cancer cells, which is likely attributable to inhibition of Cdc2-Tyr-15 phosphorylation and p21(Cip1) expression. Tyrosine cyclin dependent kinase 1 Homo sapiens
3 Because significant dephosphorylation of Cdc2-Tyr-15 and down-regulation of p21(Cip1) occur at least 24 h after Herceptin treatment, we investigated whether 24 h Herceptin pretreatment will render ErbB2-overexpressing breast cancer cells more sensitive to Taxol-induced apoptosis compared with the simultaneous treatment of Herceptin plus Taxol. Tyrosine cyclin dependent kinase 1 Homo sapiens
4 Thus, Herceptin treatment of ErbB2-overexpressing cells can inhibit ErbB2-mediated Cdc2-Tyr-15 phosphorylation and p21(Cip1) up-regulation, which allows effective p34(Cdc2) activation and induction of apoptosis upon Taxol treatment. Tyrosine cyclin dependent kinase 1 Homo sapiens