Alteration of gene expression in rat mammary tumors induced by N-methyl-N-nitrosourea

✍ Scribed by Lindon H. Young; Xiaoqi Yang; Jeffrey M. Voigt

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 947 KB
• Volume: 15
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199604)15:4<251::aid-mc2>3.0.co;2-j

✦ Synopsis

Rodents are susceptible to the effects of chemical carcinogens and have been widely used in the study of mammary-gland carcinogenesis. However, little information is available regarding specific phenotypic changes that occur during mammary-gland carcinogenesis. In this study, subtraction hybridization was used to identify specific genes whose expression in N-methyl-N-nitrosourea (MNU)-induced rat mammary tumors had been altered. mlRNA isolated from normal rat mammary tissue and tumors induced by treatment of 50-d-old female rats with M N U (50 mg/kg) was used to produce normal and tumor cDNA libraries. Total inserts prepared from each cDNA library were used to produce a subtracted tumor-normal probe. Differential screening of the tumor library with the subtracted probe and normal cDNA yielded 20 clones that appeared to be differentially expressed. Northern analysis of mRNA isolated from normal mammary tissue and tumor tissue confirmed that four of these clones were differentially expressed. The expression of clones 4 and 15 was greatly increased (1 3fold and t:enfold, respectively) in most MNU-induced mammary tumors, whereas the expression of clones 10 and 27 WiaS decreased (13-fold and fourfold, respectively). Sequence analysis revealed that clones 15 and 27 were highly homologous to calcyclin and a cDNA isolated from HL-60 cells, respectively. The differential expression of clones 4 and 10 was due to the presence within these clones of retroviral sequences and a fragment of transferrin, respectively. These clones may represent markers useful for studying the development of MNUinduced mammary-gland neoplasias.