Date of Award

8-2026

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Biology

Thesis Sponsor/Dissertation Chair/Project Chair

Carlos Molina

Committee Member

Lisa Hazard

Committee Member

Matthew Aardema

Abstract

Melanoma is an aggressive form of skin cancer characterized by rapid progression, metastatic potential, and the frequent development of resistance to targeted therapies. Although the Inducible cAMP Early Repressor (ICER) has been identified as a potential tumor suppressor in melanoma, the molecular mechanisms underlying its role in tumor progression remain poorly understood. Building upon the transcriptomic findings of Wheelan et al. (2025), this study investigates the relationship between ICER and ten candidate genes (gdf6a, pdgfra, col4a4, fgfr2, pdgfrb, cdkn1a, fgf5, akt1, met, and notch3) associated with BMP signaling. Quantitative polymerase chain reaction (qPCR) was used to compare gene expression between EGFP-expressing melanoma cells (446) and wild-type ICER-expressing melanoma cells (447). In addition, the sensitivity of both cell lines to the BRAF inhibitor PLX4720 was evaluated by measuring melanoma cell viability as a percentage of untreated controls. qPCR analysis demonstrated that gdf6 was overly expressed in 447 cells, with an approximately 1.5-fold change, whereas cdkn1a and notch3 showed fold-change values below 1, indicating no overexpression relative to the housekeeping gene rpl7. These findings suggest that gdf6 may contribute to the increased aggressiveness and invasiveness observed in 447 melanoma cells. Moreover, PLX4720 treatment demonstrated that 447 cells retained a higher percentage of viable cells than 446 cells, indicating greater resistance to BRAF inhibition and supporting their more aggressive phenotype. Collectively, these findings identify gdf6 as a potential contributor to melanoma progression and suggest that increased gdf6 expression, together with enhanced resistance to PLX4720, may underlie the aggressive behavior of 447 melanoma cells. Further investigation into the regulatory relationship between ICER and gdf6, as well as the mechanisms linking gdf6 to resistance against BRAF inhibitors, may facilitate the development of more effective targeted therapies for melanoma.

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