BACKGROUND: Herceptin is a humanized antibody that binds to the product of the HER-2 oncogene. Clinical studies have indicated that treatment with Herceptin may slow disease progression in tumors expressing high levels of the HER-2 antigen. However, the mechanism of this action is not known. METHODS: Four different cell lines were used that had different levels of HER-2 expression. Treated and nontreated cells were analyzed for DNA strand breaks and cell cycle perturbation using standard flow cytometry methods. RESULTS: In this study we found that cell lines expressing high levels of HER-2, when treated with Herceptin, exhibited marked increases in DNA strand breaks as measured by the TUNEL assay, and that these cells also exhibited slowed growth. BT-474 and SKBR-3 cell lines, both of which express high levels of the HER-2 antigen, had significant increases in labeled nucleotide expression at 3 and 6 day time points following exposure to Herceptin at a concentration of 10 microg/ml. Similar treatment of MCF-7 and MDA-231 cell lines, both of which express low levels of HER-2, had little effect on the level of labeled nucleotide expression at either the 3 or 6 day time points. Following 4 days of Herceptin treatment, BT-474 and SKBR-3 cell lines had significant decreases in the percentage of cells in the S phase of growth. This effect was not seen in either the MCF-7 or MDA-231 cell lines. CONCLUSION: Herceptin has a biological effect only on cells that contain high levels of HER-2. This effect is a decrease in cell proliferation that is coincident with, and may be caused by an increase frequency of DNA strand breaks.
BACKGROUND:Herceptin is a humanized antibody that binds to the product of the HER-2 oncogene. Clinical studies have indicated that treatment with Herceptin may slow disease progression in tumors expressing high levels of the HER-2 antigen. However, the mechanism of this action is not known. METHODS: Four different cell lines were used that had different levels of HER-2 expression. Treated and nontreated cells were analyzed for DNA strand breaks and cell cycle perturbation using standard flow cytometry methods. RESULTS: In this study we found that cell lines expressing high levels of HER-2, when treated with Herceptin, exhibited marked increases in DNA strand breaks as measured by the TUNEL assay, and that these cells also exhibited slowed growth. BT-474 and SKBR-3 cell lines, both of which express high levels of the HER-2 antigen, had significant increases in labeled nucleotide expression at 3 and 6 day time points following exposure to Herceptin at a concentration of 10 microg/ml. Similar treatment of MCF-7 and MDA-231 cell lines, both of which express low levels of HER-2, had little effect on the level of labeled nucleotide expression at either the 3 or 6 day time points. Following 4 days of Herceptin treatment, BT-474 and SKBR-3 cell lines had significant decreases in the percentage of cells in the S phase of growth. This effect was not seen in either the MCF-7 or MDA-231 cell lines. CONCLUSION:Herceptin has a biological effect only on cells that contain high levels of HER-2. This effect is a decrease in cell proliferation that is coincident with, and may be caused by an increase frequency of DNA strand breaks.
Authors: Sandra Zazo; Paula González-Alonso; Ester Martín-Aparicio; Cristina Chamizo; Ion Cristóbal; Oriol Arpí; Ana Rovira; Joan Albanell; Pilar Eroles; Ana Lluch; Juan Madoz-Gúrpide; Federico Rojo Journal: Am J Cancer Res Date: 2016-11-01 Impact factor: 6.166
Authors: István Molnár; Timothy Kute; Mark C Willingham; Bayard L Powell; William H Dodge; Gary G Schwartz Journal: J Cancer Res Clin Oncol Date: 2003-02-12 Impact factor: 4.553
Authors: Timothy Kute; John R Stehle; David Ornelles; Natalie Walker; Osvaldo Delbono; James P Vaughn Journal: Oncoimmunology Date: 2012-09-01 Impact factor: 8.110