(809.15) A novel cell-based Screening System Identifies Adefovir-dipivoxil as Suppressor of RET  expression in medullary thyroid carcinoma

Poster Board Number: A323

Tariq Alqahtani (King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)), Nada Alsuhebany (King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)), Mohammed Aldhaeefi (King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)), Daekyu Sun (University of arizona)

The aberrant gene expression is often associated with the progression of several cancers and hence targeting the transcriptional activation of oncogenes using small-molecules could be a potential strategy for controlling the tumor growth and development. The gain-of-function mutation in the RET proto-oncogene has been identified as the major cause for the development of medullary thyroid carcinoma (MTC), which is a part of multiple endocrine neoplasia type 2 (MEN2) syndrome. In this study we utilized a cell-based bioluminescence reporter system in which the luciferase gene expression is driven by the RET promoter to screen for drug-like molecules that potentially suppress the transcription of this gene. Using this system, we identified adefovir- dipivoxil as a transcriptional inhibitor for the RET gene, which further suppressed the endogenous RET protein expression in MTC TT cells. Consistent with this effect, adefovir-dipivoxil also inhibited RET dependent TT cell proliferation and increased apoptosis in these cells. These results highlight the potential of the cell-based screening assay to identify transcriptional inhibitors for other oncogenes.

University of Arizona
King Saud bin Abdulaziz University for Health Sciences
King Abdullah International Medical Research Center (KAIMRC)