Currently among women, breast cancer is considered to be the second leading killer as far as cancer deaths are concerned. Novel treatments and discoveries may aid in bringing down the number of deaths due to this illness. Experts from the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James) claim to put forth the first evidence that breast cancer cells can control many genes immediately by encircling their DNA and add to cancer development.
The experts have discovered a novel gene regulation and DNA behavior in breast cancer cells. This finding may have the potential to put forth a detailed insight on environmental exposure to estrogen-like compounds. The hormone estrogen was retorted in breast cancer cells by newly found gene regulation. As a result, the experts reveal that silencing of 14 genes occurred together.
“We offer a new concept in this paper for the collective regulation of gene transcription. We found that in normal breast cells, DNA looping is more flexible and brings different promoters together temporarily. But in cancer, this complex just locks up and causes long-term suppression,” affirmed Pei-Yin Hsu, a visiting scholar and researcher in Huang’s lab.
At chromosome region 16p11.2, the DNA looping event in a breast cancer cell line gene cluster was observed. In order to affirm the findings, the experts monitored normal human breast epithelial cells and two animal models. Normal-cell model was also employed to ascertain if the long-term exposure to nine estrogen-like chemicals can set-up gene silencing through this mechanism. Diethylstilbestrol, two thalates and bisphenol A (BPA) are some of the known estrogen-like chemicals that were used during the investigations.
Hsu commented, “Overall, our research shows that certain regions of the genome are silenced because the DNA has lost flexibility, and that this inflexible DNA status might be a good marker for researching environmental exposure to estrogen-like compounds.”
The researchers highlighted that the normal cells displayed different suppressive effects. In the course of the experiment, a group of four rats were exposed to BPA for 21 days. Ten genes equivalent to the region at 16p11.2 appeared to suppress simultaneously. It can therefore be concluded that exposing estrogen-like compounds continuously can silence the genes observed in the cluster forever.
A single, transcription site that lasted for only a short while was supposedly developed together by 14 gene regulatory sites in normal breast epithelial cells. However, no combined transcription site pairing was observed in breast cancer cells. In addition, the DNA loops become tangled and the entire gene complex shuts down in a dead knot.
Cancer growth seemingly boosted with elevation in expression and oncogenic activity due to this multi-gene regulatory mechanism. It is assumed that the transcription factors fasten to a site on a gene, and further the gene is vigorously transferred to another medium. It should be noted that the findings do claim that the promoter can be placed away and stay regulated rarely.
The research is published in the journal Genome Research.