Epigenetic regulation of a gene, MS-1, in cells of different metastatic potential
Date
2005-10-07
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
Breast cancer is the most common malignancy and a major cause of cancer-related death among Canadian women. Although treatment of primary breast tumours is highly successful through surgery, metastatic breast cancer is difficult to treat. Cancer progression and metastasis require the accumulation of numerous genetic and epigenetic alterations. Normal cells that acquire such alterations can transform into cancer cells, resulting in primary tumour formation. Primary tumours are a heterogeneous population, containing cells of various metastatic potentials. Cells that acquire a high potential for metastasis can spread to secondary locations. Our model system consists of two subpopulations, with different metastatic potential, derived from the same rat mammary adenocarcinoma. Using this model, a differentially expressed novel gene, termed MS-1, was discovered. Due to significant expression of this gene in the poorly metastatic subpopulation and lack of expression in the highly metastatic subpopulation, MS-1 may have involvement in metastasis suppression. Several breast cancer metastasis suppressor genes have been identified on the basis that they are down-regulated during the progression of metastasis. Epigenetic mechanisms, such as DNA methylation, account for loss of expression in several of these genes. Hypermethylation of CpG islands within gene promoters results in deacetylation of histone proteins and produces a compact chromatin structure that is unfavourable for transcription. A CpG island spans the 5’ untranslated region, exon 1 and part of intron 1 of the MS-1 gene. Our data reveals aberrant methylation patterns of this CpG island in our model. Also, MS-1 expression appears to be partially induced by both DNA methylation and histone deacetylation inhibitors. Following a screen of several cancer cell lines of various metastatic potential, it appears that the presence of DNA methylation in the CpG island of MS-1 correlates with the lack of MS-1 expression. Therefore, these results suggest that MS-1 may be silenced in cells of high metastatic potential through epigenetic mechanisms.
Description
Keywords
demethylation, CREB3L1, OASIS, histone deacetylation
Citation
Degree
Master of Science (M.Sc.)
Department
Microbiology and Immunology
Program
Microbiology and Immunology