Researchers have identified in the past that the horomone estrogen is a significant factor that can lead to the development of cervical cancer. A new project however, examined the genetic profiles of 128 clinical cases revealing an unexpected conclusion: estrogen receptors disappear in cervical cancer tumors. These results were reported in the Proceedings of the National Academy of Sciences and might have a significant impact the development of novel approaches to target the disease.
Johan den Boon, lead author of the study and researcher at the University of Wisconsin-Madison, said the team utilized gene expression profiling on 128 specimens from patients who enrolled the SUCCEED study – Study to Understand Cervical Cancer Early Endpoints and Determinants. Over 4,000 women participated in this clinical trial, in the hopes to clear the second-leading cause of cancer among women. The National Cancer Institute (NCI) and the University of Oklahoma Health Sciences Center were the entities responsible for the study.
Cervical cancers are caused by the human papillomavirus (HPV) infection; in this study, specimens were collected from 4 distinct groups — those with cervical cancer, patients with either early or advanced complications due to HPV infection and healthy individuals. Dr. den Boon noted these 4 groups allowed scientists to assess the malignancy’s full cycle: from viral infection until cancer development.
“Our top goal is to find genetic signatures that will predict what early stages of HPV infection are most likely to become cancerous, and what stages we need to worry less about,” explained Dr. den Boon.
In diseases associated with HPV there is an increase in p16 protein levels (a protein which regulates cell division). As such, researchers began to assess which other components could be behaving like p16. Dr. de Boon said: “Estrogen receptor is in the healthy cells. But as the cells become cancerous, the levels of estrogen receptor alpha crash to the point of being undetectable. P16 and estrogen were as polar opposite as you can get. When looking at similarities between the 54,000 measurements we have on the human genome, p16 would be number one and estrogen would be 54,000.”
Estrogen receptor and the genes it controls are an exquisite tool to asses cervical cancer progression. While estrogen receptor was not expressed in cancer cells it increased around the tumor to assist its development.
These findings highlight that something critical is happening between the microenvironment and the tumor itself, allowing the tumor to thrive in spite of its inability to “see” estrogen. “If we want to understand the role of estrogen, we now have to look at how the tumor and the microenvironment communicate with one another,” Dr. den Boon explained.
David Beebe, biomedical engineer, will be leading further research projects based on these novel data. “What David’s group can do is grow populations of cells in a very miniaturized state in ways that they can reach out and talk to each other through tiny channels, but yet they stay distinct,” added Dr. de Boon. The project will try to understand the biochemical signals within the tumor and its microenvironment. This might assist in the creation of therapeutics that interfere with and suppress tumor develpoment.