Abstract 2456: Overexpression of TOM40 (translocase in the outer mitochondrial membrane 40) inhibits the cell proliferation, invasion and migration abilities in ovarian cancer cell lines

Abstract

Background: Mitochondria are essential for energy conversation and cellular metabolism in eukaryotic cell. Mitochondria contain mitochondrial proteins that are encoded in the nucleus and synthesized in cytosol. Synthesized mitochondrial proteins are specially sorted by sub-mitochondrial compartment and then transported to their functional location. If mitochondrial proteins are not transported to their specific regions, it is reported that Mitochondria has a tendency to be implicated in various diseases including cancer. Mitochondria consist of mitochondrial outer membrane and inner membrane, especially, TOM complex are integrated in mitochondrial outer membrane. TOM40 is a central component of TOM complex has General import pore (GIP) to pass mitochondrial pre-protein. The goal of this study is to investigate the function of TOM40 in ovarian cancer. Methods: At first, we performed microarray to identify new target gene in ovarian cancer for nine human ovarian cancer cell line and seven human ovarian surface epithelial cell lines (HOSEs). We investigated target gene expression level in ovarian cancer cell line by RT-PCR and Western blot. To evaluate the association of target gene expression level and clinicopatholigical parameter in ovarian cancer, we carried out immunohistochemistry by using normal and ovarian cancer tissue. Second, we constructed stable DOV-13 and RMUG-S cell lines for overexpression and knock down of TOM40 protein using lentiviral system. We carried out proliferation, invasion and migration assay of each individual stable cell line. Results: We identified TOM40 as a new target gene for ovarian cancer by microarray data that was overexpressed in all nine human ovarian cancer cell lines than HOSEs. TOM40 protein level in borderline and cancer tissue was higher than normal tissue and benign tissue. TOM40 immuno-staining score of normal ovarian tissues is 1.23 (95% CI, 0.44-2.01) that compare with TOM40 immuno-staining score of benign, borderline, and epithelial ovarian tumors is 1.23 (95% CI, 0.44-2.01), 1.41 (95% CI, 0.45-2.37), 3.42 (95% CI, 2.65-4.20), and 5.04 (95% CI, 4.82-5.27), respectively. We understood TOM40 expression level of DOV-13 cells and RMUG-S cells is lower and higher than other ovarian cancer cell line. TOM40 overexpression in DOV-13 cell line inhibited the cell proliferation, invasion and migration than that of control cell line. TOM40 knock down in RMUG-S cell line induced cell proliferation, invasion and migration abilities than in control RMUG-S cell line. Conclusion: It is important to transport pathways of mitochondrial proteins, actually, the paper discussing directly association of TOM complex involving mitochondrial proteins transport and various diseases including cancer is not found. Our results suggest that TOM40 can be a role as putative tumor suppressor for ovarian cancer. Citation Format: Sol Kim, Hanbyoul Cho, Wookyeom Yang, Hyunja Kwon, Ha yeon Shin, Eunju Lee, Eun-Suk Kang, Jae-hoon Kim. Overexpression of TOM40 (translocase in the outer mitochondrial membrane 40) inhibits the cell proliferation, invasion and migration abilities in ovarian cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2456. doi:10.1158/1538-7445.AM2014-2456

The biological foundation of the genetic association of TOMM40 with late-onset Alzheimer's disease

“…Kim et al reported over expression of TOM40 reduced cell culture doubling times compared with matched controls[66]. By contrast, we found that over expression of TOM40 in HeLa cells did not alter growth rates.…”

“…TOM40 protein levels also were reduced in neurons isolated by laser capture microdissection from a mouse PD model compared with levels in neurons from unaffected controls[116]. By contrast, TOMM40 mRNA and protein levels were elevated in tumor cells [66] compared with expression levels in adjacent, non-disease tissue. Learning the biological consequences of altered TOM40 expression will contribute to a deeper understanding the role TOM40 plays in regulating mitochondrial function, and possible new insights to the pathogenesis of these diseases..…”