The Role of the RAS Tumor Suppressor, Lysyl Oxidase, in Breast Cancer Development and Progression.
Abstract
This project sought to analyze, in breast cell lines and normal and neoplastic human breast tissue, the pattern and level of expression lysyl oxidase messenger RNA. Lysyl oxidase expression acts as a suppressor of the transforming activity of the ras oncogene in mouse cells. The expression of normal ras was also determined. Reverse transcriptase-polymerase chain reaction (RT-PCR) for cellular RNA, and in situ RT-PCR on sections of fixed, paraffin-embedded breast tissue was employed. Human cancer cell lines were also transfected with a lysyl oxidase expression plasmid and examined for changes in cell growth and tumorigenic potential. Lysyl oxidase message expression was lost or severely decreased in human breast cancer cell lines. There was no corresponding increase in the expression of ras message. Both lysyl oxidase and ras were expressed in the ductal epithelium and acinar epithelium of normal breast. Expression was also detected in stromal fibroblasts, endothelial cells, and lymphocytes. In ductal carcinoma, lysyl oxidase expression was absent in some cases, patchy in others, and sometimes appeared unchanged. The expression of ras in ductal epithelium did not vary significantly between normal and cancerous tissue. A lysyl oxidase-transfected cancer cell line had a reduced growth rate and a less transformed appearance.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1997
- Accession Number
- ADA349460
Entities
People
- Sara Contente
Organizations
- Henry M. Jackson Foundation for the Advancement of Military Medicine