Contribution of CXCL10 in HER2-positive Breast Cancer
HER2-positive breast cancer is a type of breast cancer that tests positive for an overabundant amount of a protein called human epidermal growth factor receptor 2 (HER2), which leads to to abnormal cancer phenotypes. HER2 is critical for normal cellular processes, however, when the HER2 gene is amplified, or its protein is overexpressed, it can cause over-phosphorylation of HER2 which leads to tumor initiation and the progression in breast cancer. We have discovered the deletion of inhibitor of growth 4 (ING4) is prevalent in HER2-positive breast cancer. The highest deletion rate at 28.4%. However, ING4’S function in HER2-positive breast cancer is unknown. CXCL10, a chemokine, induces migration of immune cells to their focal sites. We hypothesize CXCL10 might be responsible for migrating cancer cells. However, CXCL10’s function in HER2-positive breast cancer is unknown. We hypothesize that CXCL10 induces activation of HER2 through CXCR3, and CXCL10 migration is dependent on ING4. Our two cancer cell lines are SKBR3 and MDA-mb-453, which are both HER2 overexpressed. We used modified cell lines to test the effects ING4 has during our experiments. V2 is the vector control for V2H1, the ING4 deletion and PMP is the vector control for PMP-ING4, which has overexpressed ING4. We performed a Western Blot to quantify proteins. We are testing activation of HER2 by looking at its phosphorylated form. Our first conclusion from our data is that ING4 status affects phosphorylation of HER2 resulting in increased activation. In other words, when ING4 is not present, there is more phosphorylation. Related to patient data, we can see patients who do not have ING4 show overly active HER2 which suggests those overly active HER2 tumors are more aggressive. Our second conclusion is that CXCL10 increases phosphorylated HER2. We performed a migration assay to test for our phenotype. Our phenotype results demonstrate more migration when ING4 is not present. We can see the grave impact ING4 tumor suppressor gene has as a Gatekeeper. Gatekeepers are genes which directly regulate tumor growth, proliferation, migration, or apoptosis. The inactivation of ING4 genes could contribute directly to cancer development and progression.