OBJECTIVES: Overexpression or constitutive activation of epidermal growth factor receptors (EGFR) is involved in growth of human cancers. We investigated effects of EGFR and HER-2 blockade in colon cancer cell lines using cetuximab and trastuzumab, with the aim of developing novel approaches to cancer therapy. MATERIALS AND METHODS: We studied effects of treatment on cell growth, cell cycle distribution, induction of apoptosis, changes in EGFR and HER-2 mRNA-protein expression and EGFR and HER-2 gene copy number in Caco-2, HT-29 and HCT-116 cells. RESULTS: Treatment of cells resulted in no effect in one of the three cell lines and in inhibition of cell proliferation in a time- and dose-dependent manner in the other two, with modulation of EGFR and HER-2 mRNA and protein levels. Differences in sensitivity to cetuximab and trastuzumab were observed. Treatment induced specific changes in cell cycle distribution in both cell lines affected, while apoptosis was not increased. Fluorescence in situ hybridization analysis revealed abnormal copy number of two genes resulting from aneuploidy; this was not responsible for different sensitivity to combination between the two cell lines. CONCLUSIONS: Targeting EGFR and HER-2 simultaneously could have useful applications in colorectal cancer treatment. To improve pharmacological efficacy of cetuximab and trastuzumab combination, molecular mechanisms involved in their activity need to be elucidated.
OBJECTIVES: Overexpression or constitutive activation of epidermal growth factor receptors (EGFR) is involved in growth of humancancers. We investigated effects of EGFR and HER-2 blockade in colon cancer cell lines using cetuximab and trastuzumab, with the aim of developing novel approaches to cancer therapy. MATERIALS AND METHODS: We studied effects of treatment on cell growth, cell cycle distribution, induction of apoptosis, changes in EGFR and HER-2 mRNA-protein expression and EGFR and HER-2 gene copy number in Caco-2, HT-29 and HCT-116 cells. RESULTS: Treatment of cells resulted in no effect in one of the three cell lines and in inhibition of cell proliferation in a time- and dose-dependent manner in the other two, with modulation of EGFR and HER-2 mRNA and protein levels. Differences in sensitivity to cetuximab and trastuzumab were observed. Treatment induced specific changes in cell cycle distribution in both cell lines affected, while apoptosis was not increased. Fluorescence in situ hybridization analysis revealed abnormal copy number of two genes resulting from aneuploidy; this was not responsible for different sensitivity to combination between the two cell lines. CONCLUSIONS: Targeting EGFR and HER-2 simultaneously could have useful applications in colorectal cancer treatment. To improve pharmacological efficacy of cetuximab and trastuzumab combination, molecular mechanisms involved in their activity need to be elucidated.
Authors: Jamie B Spangler; Jason R Neil; Sivan Abramovitch; Yosef Yarden; Forest M White; Douglas A Lauffenburger; K Dane Wittrup Journal: Proc Natl Acad Sci U S A Date: 2010-07-07 Impact factor: 11.205
Authors: David Cunningham; Yves Humblet; Salvatore Siena; David Khayat; Harry Bleiberg; Armando Santoro; Danny Bets; Matthias Mueser; Andreas Harstrick; Chris Verslype; Ian Chau; Eric Van Cutsem Journal: N Engl J Med Date: 2004-07-22 Impact factor: 91.245
Authors: Minaxi Jhawer; Sanjay Goel; Andrew J Wilson; Cristina Montagna; Yi-He Ling; Do-Sun Byun; Shannon Nasser; Diego Arango; Joongho Shin; Lidija Klampfer; Leonard H Augenlicht; Roman Perez-Soler; Roman Perez Soler; John M Mariadason Journal: Cancer Res Date: 2008-03-15 Impact factor: 12.701