Gene expression profiles of potential 6-(4-hydroxpiperidino) naphthalen-2-ol-based selective estrogen receptor modulators in mummichogs (Fundulus heteroclitus)
LE3 .A278 2019
Bachelor of Science
Selective Estrogen Receptor Modulators or SERMs, are hormone therapy drugs used to combat hormone-positive breast cancers. Dr. Amitabh Jha and his team at Acadia have synthesized two novel 6-(4-hydroxypiperidino)naphthalen-2-ol based SERMs that have shown potential in preliminary biological studies. The mechanism of action of these drugs can be assessed through differential gene expression studies. Gene pathways of interest for these SERMs include cyclin D1, rap1gap, and foxP3. By extracting RNA from gill tissue of fish treated with the various SERMs and using quantitative PCR (qPCR) techniques, gene expression profiles can provide insight toward the mechanism of action of these SERMs. qPCR analysis showed stable expression for foxP3, rap1gap, and cyclin D1 when treated with DMSO alone. β-actin was variably expressed in the DMSO-treated fish and so was discarded as a reference gene. Elongation factor α was much more suitable, as it was stably expressed during DMSO and SERMs treatments. The transcription factor foxP3 did not vary in expression during SERMs treatment. Cyclin D1 increased in expression for both novel SERMs and 17-β estradiol at the six-hour time point, an upregulation that was maintained at 24 hours. This work is significant for the understanding of the cellular pathways modified by these drugs. This is useful for the screening of potential SERMs and synthesis of future potential SERMs, working toward better treatment options for hormone-positive breast cancers.
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