Biophysical Society Thematic Meeting - October 25-30, 2015

Polymers and Self Assembly: From Biology to Nanomaterials Poster Session II

35-POS Board 35 Mutant p53 Aggregates in Glioblastoma Cell Lines Murilo M. Pedrote 1 , Guilherme A. Piedade de Oliveira 1 , Tania C. Spohr 2 , Flavia R. Lima 2 , Jerson L. Silva 1 . 1 Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 2 Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil. Glioblastoma Multiforme (GBM) is the most common and aggressive brain tumor in humans. According to World Health Organization (WHO), it is classified as grade IV glioma. This feature is correlated with the high tumor invasiveness to the normal adjacent nervous tissue. p53 is a tumor suppressor protein which plays an essential role in preventing the development of cancer through cell cycle arrest or apoptosis in response to DNA damage. Mutations in TP53 gene is frequently associated to a high probability of cancer development. Therefore it is a great target against cancer. Studies from our group have shown that p53 aggregation into a mixture of oligomers and fibrils sequestrates the native protein into an inactive conformation, typical of a prionoid1. Furthermore, these aggregates are present in tissue biopsies of breast cancer and in several cancer cell lines such as basal cell carcinoma, breast and ovarian carcinoma. Objective: To evaluate p53 aggregation and the gain-of-function phenotype of mutated p53 in glioblastoma multiforme cell lines. Material and Methods: Primary GBM cells U87MG, U138MG, T98G and cells derived from patient biopsies (GBM11) were used to evaluate p53 transcripts and protein levels, protein aggregation assays by confocal microscopy and the response of Temozolomide treatment to the mRNA levels of p53 target genes. Results and Discussion: Mutated p53 accumulates in glioblastoma cell lines, aggregates in the perinuclear space and shows a gain-of- function by increasing O6-alkylguanine DNA alkyltransferase expression. Furthermore, glioma cells with mutated p53 (T98G and U138MG) migrates more upon scratch when compared top53 wild type. The gain-of-function of aggregated p53 in glioblastoma cell lines may explain the GBM phenotype, migration and open up new opportunities to target these cells against tumor.

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