Novel Luciferase-Based Reporter System to Monitor Activation of ErbB2/Her2/neu Pathway Noninvasively During Radiotherapy
- Department of Radiation Oncology, University of Colorado Denver School of Medicine, Aurora, CO (United States)
Purpose: To develop a split-luciferase-based reporter system that allows for noninvasive monitoring of activation of the Her2/neu pathway in vivo in a quantitative and sensitive manner. Methods and Materials: Fusion proteins of the ErbB2/Her2/neu receptor to the N-terminal fragment of luciferase and of its downstream binding partner Shc to the C-terminal fragment of luciferase have been engineered owing to the rationale that on activation and binding of the Her2 receptor molecule to Shc, luciferase function will be reconstituted. Thus, the resulting bioluminescence signals can serve as a surrogate measure of receptor activation. Results: We have shown that our reporter systems functions well in vitro in breast cancer cells and in vivo in xenograft tumors. In particular, the activities of Her2/neu in xenograft tumors could be monitored serially for an extended period after radiotherapy. Conclusions: We believe that the novel ErbB2/Her2/neu reporter we have presented is a powerful tool to study the biology of the Her2-neu pathway in vitro and in vivo. It should also facilitate the development and rapid evaluation of new Her2/neu-targeted therapeutic agents.
- OSTI ID:
- 21491560
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 79, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2010.08.001; PII: S0360-3016(10)03030-0; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
Similar Records
Molecular Imaging of the ATM Kinase Activity
Design and development of PEGylated liposomal formulation of HER2 blocker Lapatinib for enhanced anticancer activity and diminished cardiotoxicity
Related Subjects
BIOLUMINESCENCE
DRUGS
LUCIFERASE
MAMMARY GLANDS
MONITORING
NEOPLASMS
RADIOTHERAPY
RECEPTORS
BODY
DISEASES
EMISSION
ENZYMES
GLANDS
LUMINESCENCE
MEDICINE
MEMBRANE PROTEINS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
OXIDASES
OXIDOREDUCTASES
PHOTON EMISSION
PROTEINS
RADIOLOGY
THERAPY