Study On The Role Of Bacp/Nlp In Tumorigenesis By Using Transgenic Technology

Bacp/Nlp (Brcal associated centrosome protein/Ninein-like protein) is a novel centrosome associated protein. Recently, we found that Bacp/Nlp was a potential oncogene. In order to research into the relationship between Bacp/Nlp and tumorigenesis, we generated Bacp/Nlp transgenic mice by using transgenic technology. After identifying the Bacp/Nlp expressing transgenic mice, we carried out a series of experiments at animal and cell levels to investigate the possible role of Bacp/Nlp in tumorigenesis.We first carried out animal experimental studies to investigate the role of Bacp/Nlp in governing susceptibility to tumorigenesis under different conditions in vivo, and found that the transgenic mice without any treatment showed a nearly 20% incidence of spontaneous rumors, including breast cancer, carcinoma in situ of testicle, and a suspected ovary cancer. In contrast, none of the wild type mice showed any spontaneous tumors. In addition, we treated the Bacp/Nlp transgenic mice and their corresponding control mice with two types of DNA damage agent, including chemical carcinogen DMBA and physical carcinogen ionizing radiation (IR) to examine their tumorigenesis. In these studies, Bacp/Nlp transgenic mice showed increased tumor susceptibility to DNA damage agents.In the DMBA group, all mice were injected with a single i.p. dose of DMBA at 10-14days of age. At 42 weeks after DMBA injection, all animals were killed for pathological examination. About 45.8% of Bacp/Nlp transgenic mice were detected to have tumors, including lung adenocarcinoma, gastrointestinal stromal tumor, and squamous cell carcinoma, which were about 3 times as many as the control ones (15%).In the IR group, all mice were subjected to continued three dose of 3 Gy of X-Ray radiation every 6 days. At 32 weeks after irradiation, all mice were killed for pathological examination. The incidence of tumor of transgenic mice and control mice was 60% and 42%, respectively. The predominant tumor type in this group was lymphoma.In order to comprehend how Bacp/Nlp promoted tumorigenesis, we isolated MEF (mouse embryo fibroblast) cells from transgenic and the control mice to examine their biological phenotypes in vitro. We observed the transgenic MEF cells grew faster than the control MEF cells, and the former had a higher colony formation rate than the latter. Moreover, the transgenic MEF cells exhibited increased adhesion ability compared with the control MEF cells, but they did not showed obvious differences in in vitro invasion and migration assays. We also found centrosome amplification in transgenic MEF cells. After UV and X-Ray radiation, the apoptotic rate of transgenic MEF cells was less than the control MEF cells, which indicated that expression of Bacp/Nlp enhanced the anti-apoptotic ability of MEF cells.In summary, our findings indicated that Bacp/Nlp has strong ongenic property and promotes the tumorigenesis. The mechanisms might be through accelerating cell growth, promoting anti-apoptotic ability of cells to all kinds of DNA damage agents, and inducing centrosome abnormality that cause genome instability.