Our lab is broadly interested in addressing three questions:
(1) What are the genetic and epigenetic changes by which gene expression is regulated during tumor development?
(2) How do the genes showing expression differences in tumors compared to normal cells affect tumor progression?
(3) What are the functions of these genes in the cells?
Breast cancer is the most common cancer in women. It can be classified according to molecular and histological subtypes with the most aggressive behavior usually being attributed to the triple negative (TN) subtypes, characterized by loss of estrogen, progesterone, and Her2 receptor expression. We identified some genes targeted by the BRCA1 gene and found one gene that is involved in TN breast cancer progression and survival of the patients. We are investigating its role in breast cancer development and whether it has a role in drug resistance in the cells.
Epigenetic changes are heritable changes in gene expression patterns that do not involve alterations in the nucleotide sequence of DNA. DNA methylation is a well-known mechanism for epigenetic gene silencing in mammals. CpG islands are usually unmethylated in normal cells. The methylated state of a CpG island usually refers to transcriptionally repressed promoters. Tumor suppressor genes (TSG) may become inactivated during tumorigenesis through hypermethylation of associated CpG islands, providing several survival advantages.
We identified many genes by utilizing microarray expression profiling of AZA-treated breast cancer (BC) and non-tumorigenic breast (NTB) cell lines. Detection of hypermethylated DNA as a cancer biomarker is advantageous regarding the stable nature of DNA, ease of detection, and specificity of DNA hypermethylation for tumor cells. One of these genes, TAGLN is a frequently hypermethylated gene and a potential future biomarker for breast cancer. We are investigating its potential as a circulating cell-free DNA (cfDNA) diagnostic biomarker in breast and other cancers.