Tags

Type your tag names separated by a space and hit enter

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.
Cancer Res. 2001 Jun 15; 61(12):4892-900.CR

Abstract

We 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 down-regulation of the erbB-2 receptor in all erbB-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.

Authors+Show Affiliations

Genetics Department, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20889, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11406568

Citation

Cuello, M, et al. "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." Cancer Research, vol. 61, no. 12, 2001, pp. 4892-900.
Cuello M, Ettenberg SA, Clark AS, et al. 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. Cancer Res. 2001;61(12):4892-900.
Cuello, M., Ettenberg, S. A., Clark, A. S., Keane, M. M., Posner, R. H., Nau, M. M., Dennis, P. A., & Lipkowitz, S. (2001). 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. Cancer Research, 61(12), 4892-900.
Cuello M, et al. 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. Cancer Res. 2001 Jun 15;61(12):4892-900. PubMed PMID: 11406568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Cuello,M, AU - Ettenberg,S A, AU - Clark,A S, AU - Keane,M M, AU - Posner,R H, AU - Nau,M M, AU - Dennis,P A, AU - Lipkowitz,S, PY - 2001/6/19/pubmed PY - 2001/7/13/medline PY - 2001/6/19/entrez SP - 4892 EP - 900 JF - Cancer research JO - Cancer Res VL - 61 IS - 12 N2 - We 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 down-regulation of the erbB-2 receptor in all erbB-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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/11406568/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_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11406568 DB - PRIME DP - Unbound Medicine ER -