High Expression of Cyclin D1 and p21 in N-Nitroso-N-Methylurea-Induced Breast Cancer in Wistar Albino Female Rats

Document Type : Research Article


1 . Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University (TUM), Tehran, Iran

2 . Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran


N-nitroso-N-methylurea (NMU) induces breast cancer in rodents, particularly in rats. This model of breast cancer is very similar to human breast cancer. As a continuation of our recent work, we investigated the expressions of cyclin D1 and p21 in NMU-induced breast cancer of Wistar Albino rats. Materials and Methods:In this experimental study, mammary carcinoma was induced in female Wistar Albino rats by a new protocol which included the intraperitoneal injection of NMU (50 mg/kg) at 50, 65, and 80 days of the animal’s age. The animals were weighed weekly and palpated in order to record the numbers, location, and size of tumors. Subsequently tumor incidence (TI), latency period (LP), and tumor multiplicity (TM) were reported. About four weeks after the tumor size reached 1.5 cm3, rats were sacrificed. Cyclin D1 and p21 expressions in tumors and normal mammary glands from normal rats were measured by reverse-transcription polymerase chain reaction (RT- PCR) and Western blot analysis. Statistical analysis of the data was performed using SPSS software version 16.0. Results:The efficiency of tumor induction was 65%, LP was 150 days, and a TM of 1.43 ± 0.53 per rat was noted. RT-PCR and Western blot data indicated significant (p < 0.05) induction of both cyclin D1 and p21 expressions in rat mammary tumors compared with normal tissue from the control group. Conclusion:These results indicate an efficient mammary tumor induction protocol for this type of rat, which is accompanied by an increase in cyclin D1 and p21 expressions.