Researchers from the University of Texas Southwestern Medical Center in Dallas, led by Dr. W. Lee Kraus, identified a cross-talk between inflammatory and estrogen effects on the growth of breast cancer. The study entitled “TNFa Signaling Exposes Latent Estrogen Receptor Binding Sites to Alter the Breast Cancer Cell Transcriptome” was published in the journal Molecular Cell.
Breast cancer is the second leading cause of cancer-related death among women in the United States with 12.3 percent expected to be diagnosed with breast cancer during their lifetime, according to statistics from the National Cancer Institute (NCI).
About 65% of breast cancers have a significant number of estrogen hormone receptors (regulators of gene transcription) and their growth is stimulated by this hormone (ER positive). These types of cancers can be targeted by anti-hormone therapies such as Tamoxifen that lowers their response to estrogen.
The immune response is another important player in tumor growth as immune cells can produce a cytokine called tumor necrosis factor alpha (TNFa), a pro-inflammatory molecule. While estrogen stimulates proliferation of breast cancer cells, TNFa can have either proliferative or anti-proliferative effects depending on the tumor type.
Researchers studied whether estrogen combined with TNFa affects the biology of breast cancers. The results showed that TNFa completely blocked the potent mitogenic response to estrogen of certain ER-positive breast cancer cell lines. TNFa changed estrogen receptor binding to the genome creating a new gene transcription landscape, different from the one generated by either agent alone. High-level expression of synergistically regulated genes is associated with good outcomes in some types of breast cancers, but poor outcomes in other types. These data demonstrate the different impact of inflammation in different types of breast cancer and may help to predict how tumors will react to therapies, thus opening the path to new tumor treatment possibilities.
“Our study uncovered the molecular mechanisms that alter the expression of the new set of genes in response to estradiol and TNFα, and identified potential target genes for future therapy,” said Dr. Kraus. “Since the altered pattern of gene expression can predict outcomes in breast cancer, there are important diagnostic and prognostic implications,” he added.