| First Author | Hwang SK | Year | 2010 |
| Journal | PLoS One | Volume | 5 |
| Issue | 9 | PubMed ID | 20824095 |
| Mgi Jnum | J:165023 | Mgi Id | MGI:4836092 |
| Doi | 10.1371/journal.pone.0012535 | Citation | Hwang SK, et al. (2010) Suppression of lung tumorigenesis by leucine zipper/EF hand-containing transmembrane-1. PLoS One 5(9) |
| abstractText | BACKGROUND: Leucine zipper/EF hand-containing transmembrane-1 (LETM1) encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. However, a previous study demonstrated that LETM1 served as an anchor protein for complex formation between mitochondria and ribosome, and regulated mitochondrial biogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Therefore, we examine the possibility that LETM1 may function to regulate mitochondria and lung tumor growth. In this study, we addressed this question by studying in the effect of adenovirus-mediated LETM1 in the lung cancer cell and lung cancer model mice. To investigate the effects of adenovirus-LETM1 in vitro, we infected with adenovirus-LETM1 in A549 cells. Additionally, in vivo effects of LETM1 were evaluated on K-ras(LA1) mice, human non-small cell lung cancer model mice, by delivering the LETM1 via aerosol through nose-only inhalation system. The effects of LETM1 on lung cancer growth and AMPK related signals were evaluated. Adenovirus-mediated overexpression of LETM1 could induce destruction of mitochondria of lung cancer cells through depleting ATP and AMPK activation. Furthermore, adenoviral-LETM1 also altered Akt signaling and inhibited the cell cycle while facilitating apoptosis. Theses results demonstrated that adenovirus-LETM1 suppressed lung cancer cell growth in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: Adenovirus-mediated LETM1 may provide a useful target for designing lung tumor prevention and treatment. |
