Page 84 - D. Cancer biology

[D. Cancer biology-56]

Mitochondria associated genes alteration in GBM induces

Avastin resistance

Haseo Ryu¹, Sung Soo Kim¹, Jong Bae Park¹˙*

¹Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang

10408, Republic of Korea

Glioblastoma(GBM) is the most common form of malignant brain cancer in adults. GBM tumor cells predictably
result in high rates of early recurrence even when combination therapeutic like anti-angiogenic bevacizumab (Avastin)

is treated to GBM patients. In order to understand mechanism underlying avastin resistance in GBM, we made GBM

mouse models by injecting U87 MG (human GBM Tumor cell line) orthotopically. We observed that the cancer in
the mouse model temporarily shrink but was found to recur by drug resistance in 6 weeks after avastin treatment
compared to vehicle treated mouse model of 4 weeks life span. Proteomics data described gene expression

associated mitochondria gene module was upregulated in avastin resistance models. To find the critical mitochondria
associated gene for GBM recurrence, we made mito matrix-V5-APEX2 expressing U87 MG cell line and injected

these cells to nude mouse brain. The samples of each group were pulled down using biotin labeled agarose bead.
APEX2 specific labeled samples were then used to perform proteomics analysis. Proteomics analysis revealed that

mitochondria related genes SQRDL; SQOR and MCU were highly upregulated in avastin resistance model. Our
results suggest that targeting these genes may become an effective therapeutic strategy.