Titles and Affiliations
Professor of Pharmacology and Chemical Biology
Director of Education, Women’s Cancer Research Center
Magee Women’s Research Institute
University of Pittsburgh Cancer Institute
Research area
Understanding the biology of invasive lobular carcinoma, a common but understudied form of breast cancer.
Impact
Invasive lobular carcinoma (ILC) is a type of invasive breast cancer that originates in the milk-producing glands of the breast called lobules and accounts for 10 to 15 percent of diagnoses. The key difference between ILC and invasive ductal cancer (IDC), is the loss of E-cadherin, a protein that is present on the surface of cells and mediates attachment to other cells. How this molecular hallmark of ILC drives disease function is still an open research question.
Progress Thus Far
The team has developed an innovative new laboratory model in an attempt to “switch” an ILC tumor into an IDC tumor by restoring E-cadherin expression. In doing so, the team aims to identify characteristics in ILC that are driven by changes other than E-cadherin levels. Preliminary results indicate that overexpression of E-cadherin in ILC alone is not sufficient to “switch” subtype, implying there may be additional factors that drive biological and clinical differences between the two.
They have further discovered a protein called AP-2B, which controls the activity of many genes, is present at much higher levels in ILC tumors. Using laboratory models, they showed that lowering AP-2B levels makes lobular cancer cells stop growing and even die, suggesting AP-2B helps ILC cells survive and may be a critical driver of ILC development.
What’s next
In the coming year, the team will take a closer look at how AP-2B is expressed in normal breast tissue, benign breast lesions, and invasive breast cancer and how it may overlap with other important cancer biomarkers. They will further test whether additional AP-2B can protect lobular breast cells from dying when they lose E-cadherin. Their studies will provide insights into how AP-2B drives ILC and whether it could be a future treatment target.
Biography
Steffi Oesterreich, PhD is Professor of Pharmacology and Chemical Biology and Director of Education, Women’s Cancer Research Center at the University of Pittsburgh. The main interest of Dr. Oesterreich’s research is to further our understanding of hormone action in women’s cancer for improved diagnosis and endocrine treatment. Her studies have focused on breast cancer and in receptor action in ovarian cancer. Her lab studies how the estrogen receptor (ER) functions, how its activity is regulated by diverse signaling pathways and through coregulator proteins, and how these mechanisms are perturbed in cancer cells. The Oesterreich lab is interested in novel concepts of ER action, such as its role in repression of gene transcription and its role in epigenetic marks in the genome. Her lab also has a strong interest in situ and invasive lobular disease, with a focus on estrogen and antiestrogen response. In her role as Director of Training in the Women’s Cancer Research Center, she is interested in providing outstanding training opportunities to the next generation of women’s cancer researchers.
