Neuroblastoma (NBL) is the 4th most common pediatric tumor. Globally it constitutes 8-10% of all childhood cancers and is responsible of approximately 15% of all pediatric cancer deaths. It remains a challenge for pediatric oncologists, since long term survival for disseminated NBL is only less than 40%. Cancer cells' resistance to therapies might be one of the reasons for the failure in treatment; therefore there is an urge for finding novel treatment options. In this study we focused on HER4 and its role in neuroblastoma cell line CHP134. Results show that HER4 knockdown caused a significant decrease in cell proliferation. Also HER4 knockdown causes a decrease in tumorigenic potential. HER4 knockdown cell lines showed a slightly increase in sub G1 population when compared to nonsense control after drug treatment, suggesting that HER4 knockdown might be increasing chemo-sensitivity. We also found that different culture conditions affected HER4 expression. Monolayer culture showed an increase in HER4 expression as cell density increased, for sphere condition we obtained an up-regulation of HER4 when compared to monolayer culture. HER4 knockdown in sphere culture also promoted an increase in cleaved PARP, a marker of apoptosis, suggesting that HER4 knockdown in sphere condition increased apoptosis. From our results we propose that HER4 might be a therapeutic target for NBL treatment in the future. Further investigation is still required to understand how HER4 provides protection against stress.
This presentation is supported by the National Cancer Institute through the U54 CA096297/CA096300: UPR/MDACC Partnership for Excellence in Cancer Research Training Program. For more information, please contact Arianexys Aquino-López at email@example.com.
Researchers should cite this work as follows: