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Low-dose ionizing radiation (LDIR) induces hormesis, exerts an adoptive effect on normal mammalian cells and stimulates cell proliferation; however, this effect is absent in cancer cells. Little is known on the molecular mechanisms underlying this differential response between normal and cancer cells. In the present study, it was demonstrated that the human prostate cancer cell line PC-3 and the normal prostate cell line RWPE-1 exhibited differential biological responses to LDIR. Through cell cycle analyses, it was demonstrated that LDIR inhibited cell growth and arrested the cell cycle at the S and G2/M phases in PC-3 cells, but not in RWPE-1 cells. Using western blotting, it was demonstrated that LDIR at 75 mGy induced the expression of ataxia-telangiectasia mutated (ATM) protein in PC-3 as well as RWPE-1 cells. However, the ATM̸p21 pathway was activated in PC-3, but not in RWPE-1 cells. Although the expression of p53 was not affected by 75 mGy LDIR in RWPE-1 cells, the ATM̸p21 pathway was activated when RWPE-1 cells lost p53 function. In addition, when using ATM inhibitors, the ATM̸p21 pathway was inactivated in both cell lines, and the LDIR-induced cell proliferation inhibition was also abolished. These findings suggested that the ATM/p21 pathway directly participated in the LDIR-induced cell proliferation inhibition in p53null type prostate tumor cells, whereas this mechanism was absent in normal prostate cells. Thus, p53 may affect cell stability following LDIR, and plays a crucial role in regulating the ATM/p21 pathway activated by LDIR.

Breast cancer is the most common carcinoma among Chinese women. Interferon α (IFNα) has been used to treat various types of cancer, including breast cancer, but its antitumor activity is relative low, which significantly hinders its clinical application. In this study, we utilized a Ph.D.-12 peptide library screening system to identify a short peptide that specifically binds to MCF-7 breast cancer cells. By fusing the MCF-7 binding peptide (MBP) to the C-terminus of IFNα, we constructed an engineered IFNα-MBP fusion molecule (IMBP), and applied this novel fusion protein to the treatment of breast cancer. We found that IMBP exhibited significantly higher activity than wild-type IFNα in inhibiting cell growth and inducing cell apoptosis. Additionally, IMBP potentiated the therapeutic efficacy of doxorubicin-based breast cancer chemotherapy via the activation of cell cycle arrest and cell apoptosis pathway genes including p53, p21, CDK2, cyclin A, caspase 9, Bcl-2 and Bax. The enhanced activity of the synthetic IMBP was also associated with the activation of signal transducer and activation of transcription 1 (STAT1) pathway target genes (STAT1, IFIT1, IFITM1 and MX1). This study evaluated the potential value of the synthetic IMBP as a novel anti-breast cancer agent.

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.

To evaluate whether S100A11 could be considered to be a novel diagnostic marker in breast carcinoma, the method of differential proteomics, Western blotting, and immunohistochemistry were used to detect the expression pattern and subcellular localization of S100A11. Statistical analyses indicated that specific up-regulated of A100A11 did not correlate with other prognostic factors such as age, tumor size, grade and stage, ER, PR, HER-2 and nodal status. Our data support that S100A11 is a novel diagnostic marker in breast carcinoma. Analysis of S100A11 expression in breast cancer may be an effective tool help in detection of early-stage breast cancer.