Shaun Karakkattu
Shaun Karakkattu
Helios Scholar

School: Vanderbilt

Hometown: Mesa, Arizona

Mentor: Michael Berens, PhD

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Investigating the role of steroid hormone receptors in glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most aggressive and common type of primary brain tumor. Patients with GBM have a median survival rate between 12-14 months. There are sex-based differences that exist in the occurrence of GBM with men having a 60% higher chance of developing a tumor indicating raising the prospect that differences in the function of estrogen receptor beta (ERβ), a known tumor suppressor, may influence tumor progression in GBM. We hypothesized that 17β-estradiol (receptor ligand)  and IGF-1, estrogen receptor agonist, promote sex-based differences in ERβ relocation to the nucleus affecting transcriptional events which inhibit the proliferation of GBM cells. 17β-estradiol and IGF-1 were used to treat male and female patient-derived GBM cell lines and OVCAR-3, an ovarian cancer cell line. After treatment with 0-15 uM of 17β-estradiol or 0 to 100 ng/mL of IGF-1 for 48 to 72 hrs, cell viability was analyzed through a CellTiter-Glo® 2.0 Cell Viability Assay and the rate of cell proliferation was analyzed through a CellTiter 96® AQueous One Solution Cell Proliferation Assay.  Cytological localization of ERβ (confocal immunofluorescence microscopy) was evaluated; no discernable sex-based differences in  ERβ nuclear localization were found. Marked sex-based differences in cell response to growth arrest by 17β-estradiol were identified: female glioma cells died, while male cells stopped growing and senesced (but did not die). In conclusion, this study presents evidence that ERβ function may indeed inhibit GBM proliferation and viability. This study presents a potential approach to the treatment of GBM. As this study continues, additional steroid hormone receptors will be tested like the androgen receptor which may also cause the inhibition of cell proliferation and viability in GBM.