Screening for ErbB Family Inhibitors to Identify Potential Cancer Therapeutics

Levitan, Samuel

Student Work

Screening for ErbB Family Inhibitors to Identify Potential Cancer Therapeutics

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Cell division is a highly regulated and complex process. Uncontrolled cell division occurs when regulators of cell proliferation escape normal functionality leading to cancerous states. Receptor tyrosine kinases (RTKs) are key drivers of signaling cascades that regulate cell division. The Epidermal Growth Factor Receptor (EGFR/ErbB) family is one class of RTKs whose dysregulation underlies numerous cancers. As such, searches for molecules that interact with, and inhibit, this RTK family have been ongoing for decades. Kekkon1 (Kek1), a transmembrane protein that is part of the leucine-rich-repeat (LRR) and immunoglobulin domain (Ig), LIG family, is an inhibitor that directly interacts with the Drosophila EGFR (dEGFR). Interestingly, Kek1 does not appear to do the same with the human EGFR/ErbB family. Given that there are human LIG proteins with extracellular regions similar to Kek1, the objective of this study was to test for possible interactions between these human LIGs and members of the RTK superfamily, specifically the ErbBs. The extracellular domains of ErbB proteins and a variety of human LIGs were produced – some under varying conditions to assess protocol. Their potential interaction was later tested via an ELEXIS assay. Early results indicate no significant interactions between LINX and the RTKs Ret and TrkA. Preliminary data also shows that a twelve-day transfection incubation results in higher protein expression than ten days for several LIGs.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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