Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2

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dc.contributor.authorCuello, M
dc.contributor.authorEttenberg, SA
dc.contributor.authorClark, AS
dc.contributor.authorKeane, MM
dc.contributor.authorPosner, RH
dc.contributor.authorNau, MM
dc.contributor.authorDennis, PA
dc.contributor.authorLipkowitz, S
dc.date.accessioned2025-01-21T01:30:49Z
dc.date.available2025-01-21T01:30:49Z
dc.date.issued2001
dc.description.abstractWe investigated whether combined treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and trastuzumab could enhance the specific killing of cells that overexpress the erbB-2 receptor. The combination resulted in an enhancement of TRAIL-mediated apoptosis in all cell lines overexpressing erbB-2 receptor compared with either reagent alone. In contrast, there was no effect in cell lines with low levels of the erb-B2 receptor. Trastuzumab treatment resulted in downregulation of the erbB-2 receptor in all erbs-2-overexpressing cell lines. Similar enhancement of TRAIL toxicity was observed when the erbB-2 receptor was down-regulated using antisense oligodeoxynucleotides. Down-regulation of the erbB-2 receptor protein by trastuzumab or antisense oligodeoxynucleotides decreased Akt kinase activation but not mitogen-activated protein kinase activation. Down-regulation of Akt kinase activity by a phosphatidylinositol 3 ' -kinase inhibitor (LY294002) also resulted in enhancement of TRAIL-mediated apoptosis, Expression of a constitutively active form of Akt kinase in an erbB-2-overexpressing cell line completely abrogated the increase in TRAIL-mediated apoptosis by trastuzumab and significantly reduced the biological effect of either reagent alone. Therefore, down-regulation of the erbB-2 receptor by trastuzumab enhances TRAIL-mediated apoptosis by inhibiting Akt kinase activity. These data suggest that the combination of trastuzumab and TRAIL may allow enhanced therapeutic efficacy and specificity in the treatment of erbB-2-overexpressing tumors.
dc.fuente.origenWOS
dc.identifier.eissn1538-7445
dc.identifier.issn0008-5472
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/96902
dc.identifier.wosidWOS:000169374100039
dc.issue.numero12
dc.language.isoen
dc.pagina.final4900
dc.pagina.inicio4892
dc.revistaCancer research
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDown-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in breast and ovarian cancer cell lines that overexpress erbB-2
dc.typeartículo
dc.volumen61
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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