14 DAY TRIAL // A team of researchers at the University of Illinois at Chicago College of Medicine, has identified a process through which a protein inside the body draws chemotherapy drugs out of the tumor cells, thus making them resistant.
Most breast cancers (70 percent) include the estrogen receptor, and most ER-positive tumors normally respond well to hormone-related therapies, like tamoxifen or aromatase inhibitors.
Jonna Frasor, assistant professor of physiology and biophysics at the UIC College of Medicine and principal investigator of the study said that sometimes, these therapies do not work so the team was focused on “a subset of ER-positive tumors that are unusually aggressive and also drug-resistant.”
According to previous studies, these aggressive ER-positive tumors contain genes that respond to estrogen as well as to cytokines (inflammatory factors).
Normally, estrogen and inflammatory proteins do not work together, as estrogen has a natural tendency to fight inflammation, so it would be rather unexpected to find these two increasing cancer's aggressiveness, Madhumita Pradhan, a student in Frasor's lab and first author of the paper said.
Frasor and colleagues chose to look at the gene for a drug-transporter protein, that gets the chemotherapy drug out of the tumor cells.
What they found was that an inflammatory protein called NfĸB worked with the estrogen receptor and increased the expression of the transporter gene.
The scientists even explained the process: there is an area on a gene called a promoter that acts like an on/off button, deciding whether or not the gene is transcribed and the protein it encodes is produced.
On the promoter there are response elements – places where molecules can attach and help turn the switch on or off.
As Frasor explains, “the estrogen receptor gets recruited to the promoter of this gene, [and] once there, the ER allows NFĸB to be recruited to its own response element.
“Once the second molecule binds, it actually stabilizes the ER and the gene is turned on to a much greater extent than with the ER alone.”
This discovery has been made in certain types of breast tumors, and it could open the way to a new therapy target, for cancer in which inflammation and estrogen promote the progression of the disease.
The study has been published in the October 8 issue of the Journal of Biological Chemistry, as the paper of the week.