Upregulated Myc Expression in N-Methyl Nitrosourea (MNU)- induced Rat Mammary Tumours

Background: The most common incident cancer and cause of cancer-related deaths in women is breast cancer.The Myc gene is upregulated in many cancer types including breast cancer, and it is considered as a potentialanti-cancer drug target. The present study was conducted to evaluate the Myc (gene and protein) expressionpattern in an experimental mammary tumour model in rats. Materials and
Methods: Thirty six Sprague Dawleyrats were divided into: Experimental group (26 animals), which received the chemical carcinogen N-methylnitrosourea (MNU) and a control group (10 animals), which received vehicle only. c-Myc oncoprotein and itsmRNA expression pattern were evaluated using immunohistochemistry (IHC) and semi-quantitative reversetranscription-polymerase chain reaction (RT-PCR), respectively, in normal rat mammary tissue and mammarytumours. The rat glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as internal control forsemi-quantitative RT-PCR.
Results: Histopathological examination of mammary tissues and tumours from MNUtreated animals revealed the presence of premalignant lesions, benign tumours, in situ carcinomas and invasivecarcinomas. Immunohistochemical evaluation of tumour tissues showed upregulation and heterogeneous cellularlocalization of c-Myc oncoprotein. The expression levels of c-Myc oncoprotein were significantly elevated (75-91%) in all the tumours. Semi-quantitative RT-PCR revealed increased expression of c-Myc mRNA in mammarytumours compared to normal mammary tissues.
Conclusions: Further large-scale investigation study is needed toadopt this experimental rat mammary tumour model as an in vivo model to study anti-cancer strategies directedagainst Myc or its downstream partners at the transcriptional or post-transcriptional level.