Retroelements and Genetic Instability in Breast Cancer
Abstract
LINE1 is a mammalian retroelement that contributes to genomic instability. The full extent of LINE-1 mobility in somatic tissues and tumors is not known. L1 expression is extremely low in most differentiated cells except for testis, but it is significantly elevated in breast malignancies. This suggests that posttranscriptional mechanisms are involved in limitation of L1 expression. We demonstrated that the use of the poly A sites located within the L1.3 genome limits the amount of full- length L1.3 mRNAs. L1 polyA signals can be functional when fragments of L1.3 element are inserted into 3' UTRs of genes. This unique attenuation mechanism helps to minimize the rate of L1 retrotransposition, but may also increase the negative impact of these events on the genome after their insertion. Human EST database searches suggest that the polyA signals may also play a role in regulation of L1 expression in a tissue and/or tumor specific manner with breast cancer tissues supporting the least efficient L1 polyadenylation. The EST data are strengthened by significant differences in the L1 RNA profiles between transiently transfected breast cancer and nonbreast cancer cell lines. These observations suggest a potential global change in the mechanism of polyadenylation process upon malignant transformation of mammary gland.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436906
Entities
People
- Prescott L. Deininger
- Victoria P. Belancio
Organizations
- Tulane University of Louisiana