Characterization of cancer hallmarks in PA28γ-/- cancer clones and A9 tumor cells

• In Event: Poster Presentation and Judging for: Biomedical; Cell & Molecular Biology; Chemistry & Biochemistry; Marine Science; Systematics & Evolutionary Biology.
  In Poster Session: Cell & Molecular Biology Poster session

Abstract

Cancers make up a diverse family of diseases, with each individual cancer following a unique pathogenesis. While this results in significant variation between cancers, there are characteristic hallmarks shared by all. Understanding the various molecular mechanisms through which cells obtain these hallmarks is important. PA28γ is a proteasome activator that stimulates the degradation of proteins in an ATP- and ubiquitin-independent manner. Elevated expression of PA28γ has been observed in various cancers. Cells deficient in PA28γ were mutagenized and selected for their acquisition of anchorage independence, a phenotype exhibited by many cancer cells. In order to determine the extent to which these mutagenized PA28γ-/- “Cancer Clones” had taken on cancer-like characteristics, this investigation examined genomic instability, sensitivity to anticancer drugs, and invasive capabilities. These hallmarks were also investigated in the A9 tumor cell line. A mutation in one or more of the H-ras, akt1, and p53 genes is common in many types of cancer. This investigation found that the genes H-ras and p53 were unaltered in A9 and PA28γ-/- Cancer Clones, however, an A5P mutation was observed in Akt1 in A9 cells. A9 cells exhibited the highest degree of genomic instability and invasiveness, while PA28γ-/- Cancer Clones exhibited a phenotype intermediate between A9 and negative controls. Neither the PA28γ-/- Cancer Clones nor A9 cells exhibited sensitivity to the anti-cancer drugs tested.  Taken together, these data suggest that A9 tumor cells exhibit cancer-like characteristics to a greater degree than PA28γ-/- Cancer Clones, however, both cell lines exhibited more cancer-like characteristics than controls.

Authors

• Estefany Zambrano, Austin College

• Bethany Bundrant, Austin College

• Lance Barton, Austin College