Molecular mechanisms of radiation resistance in doxorubicin-resistant breast adenocarcinoma cells.
Int J Oncol
; 42(5): 1692-708, 2013 May.
Article
en En
| MEDLINE
| ID: mdl-23467667
A positive response to breast cancer treatment is largely dependent on the successful combination of anticancer treatment modalities, such as chemotherapy and radiation therapy. Unfortunately, chemotherapy resistance occurs frequently. Furthermore, drugresistant tumors can become unresponsive to other antitumor therapies, and they often fail to respond to radiation therapy. The molecular structures underlying the radiation responses of chemoresistant cells and tumors are not well understood. We analyzed the effect of ionizing radiation on MCF-7 human breast adenocarcinoma cells and their doxorubicinresistant variant, MCF-7/DOX. The results demonstrated that drugresistant MCF-7/DOX cells were less susceptible to radiation-induced DNA damage and apoptosis. This was proven through gene expression profiling, lower levels of γH2AX foci upon irradiation, and altered levels of DNA repair proteins, including pATM, KU70 and RAD51. Additionally, MCF-7/DOX drugresistant cells harbored DNA polymerases with significantly low fidelity. In summary, our study revealed that drug-resistant MCF-7/DOX cells have high DNA repair potential and low-fidelity DNA polymerases, seemingly sacrificing specificity and efficiency to gain higher survival potential. In the long run, this may lead to an increased probability of mutation accumulation and further the development of an even more pronounced resistance phenotype. Therefore, this study provides a roadmap for the analysis of the roles of the DNA repair function and effectiveness, and apoptosis in response to radiation, chemotherapy and combinations of both treatment modalities.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Adenocarcinoma
/
Resistencia a Antineoplásicos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Int J Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2013
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Grecia