title: Low-dose irradiation promotes proliferation of the human breast cancer MDA-MB-231 cells through accumulation of mutant P53.
abstract: Low-dose irradiation (LDIR) has been proven to have differential biological effects on normal mammalian somatic cells and cancer cells. Our previous study showed that p53 gene status is a critical factor regulating the effect of LDIR on cancer cells. We investigated the effect of LDIR on the breast cancer cell line MDA-MB-231 that harbors a mutant p53 gene, and the normal breast fibroblast cell line Hs 578Bst. In the present study, we showed that 150 mGy LDIR pormoted growth of MDA-MB-231 cells but not Hs 578Bst cells. Through cell cycle analyses, we found that LDIR accelerated cell cycle into S phase in MDA-MB-231 cells, but did not affect the cell cycle of Hs 578Bst cells. Using western blotting, we demonstrated that the expression of CDK4, CDK6 and cyclin D1 was upregulated in MDA-MB-231 cells after LDIR. Although LDIR increased ataxia-telangiectasia mutated (ATM) level in both MDA-MB-231 cells and Hs 578Bst cells and activated ATM/p53/p21 pathway, only the mutant type of p53 (mtp53) protein in MDA-MB-231 cells was shown to be accumulated after LDIR. Using ATM inhibitor or lentivirus-mediated small interfering RNA (siRNA) to block the ATM/p53/p21 pathway in MDA-MB-231 cells, the LDIR-induced cell proliferation was abolished. When we introduced wild-type p53 (wtp53) protein into MDA-MB-231 cells, the LDIR-induced cell proliferation was also abolished. These findings suggest that normal p53 function is crucial in ATM/p53/p21 pathway activated by LDIR. The p53 status is the most probable reason leading to differential LDIR biological activities between breast tumor cells and normal breast cells.
authors.affiliation: Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Si-Jie
authors.initials: SJ
authors.lastname: Li
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xin-Yue
authors.initials: XY
authors.lastname: Liang
authors.affiliation: Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hai-Jun
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Clinical Medicine, Norman Bethane Health Science Center, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hua-Qiu
authors.initials: HQ
authors.lastname: Chen
authors.affiliation: Department of Clinical Medicine, Norman Bethane Health Science Center, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Song-Gen
authors.initials: SG
authors.lastname: Ye
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: De-Hai
authors.initials: DH
authors.lastname: Yu
authors.affiliation: Cancer Center, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jiu-Wei
authors.initials: JW
authors.lastname: Cui
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D050505:Mutant Proteins / Q000096:biosynthesis / Q000235:genetics; D011827:Radiation; D011829:Radiation Dosage; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050505:Mutant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins