Potential Mechanisms Involved in Resistant Phenotype of MCF-7 Breast Carcinoma Cells to Ionizing Radiation-Induced Apoptosis

Yan-Lin Wang (1, 2, 3) , Hong Zhang (1, 2) , Ning Li (1, 2, 3) , Xiaohu Wang (4) , Ji-Fang Hao (1, 2) , Wei-Ping Zhao (1, 2, 3)

1 Institute of Modern Physics
2 Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province
3 GSCAS - Graduate School of the Chinese Academy of Sciences
4 Tumor Hospital of Gansu Province

We investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest induced by irradiation in MCF-7 cells. X-irradiation, in particular low dose irradiation (1Gy), had a significant antiproliferative effect on the growth of MCF-7 cells. Irradiation by X-rays resulted in G1 and G2 phase arrest. However, carbon ions resulted in a significant accumulation in G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ions resulted in an approximately 3-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected in X-ray irradiation. Carbon ions caused a significant increase of p21 expression and reduction of Bax expression compared with X-rays. The data implicated that phosphorylation of BRCA1 on serine residue 1524, at least partially, is positive relation with p21 expression but negative relation with Bax expression. Together, our results suggested the phosphorylation of BRCA1 at Ser-1524 may contribute to the G2 phase arrest and be an upstream signaling involved in preventing apoptosis signaling via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

Mots clés: BRCA1; phosphorylation; MCF-7 Breast Carcinoma Cells; ionizing radiation (IR); p21; Bax; Bcl-2

Domaines: Cancer

Yan-Lin Wang, Hong Zhang, Ning Li, Xiaohu Wang, Ji-Fang Hao, et al.. Potential Mechanisms Involved in Resistant Phenotype of MCF-7 Breast Carcinoma Cells to Ionizing Radiation-Induced Apoptosis. The Seventh International Symposium on Swift Heavy Ions in Matter, Jun 2008, Lyon, France. ⟨hal-00201670⟩