TSPYL5 is involved in cell growth and the resistance to radiation in A549 cells via the regulation of p21{sup WAF1/Cip1} and PTEN/AKT pathway

Journal Article · Fri Feb 12 04:00:00 EST 2010 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2010.01.045· OSTI ID:22202378

Kim, Eun Jin; Lee, So Yong; Kim, Tae Rim; Choi, Soo Im ^[1]; Cho, Eun Wie ^[2]; Kim, Kug Chan ^[1]

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1. Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, P.O. Box 105, Yuseong, Daejeon 305-600 (Korea, Republic of)
2. Systemic Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-333 (Korea, Republic of)

TSPYL5, encoding testis-specific Y-like protein, has been postulated to be a tumor suppressor gene, and its hypermethylation is often associated with human disease, especially cancer. In this study, we report that the TSPYL5 gene was less methylated (30%) in A549 lung adenocarcinoma cells, which are relatively resistant to {gamma}-radiation, than in H460 lung cancer cells, in which the TSPYL5 gene was hypermethylated (95%); thus, the expression level of TSPYL5 is much higher in A549 cells than in H460 cells. We showed that TSPYL5 suppression with silencing RNA in A549 cells up-regulated cellular PTEN, followed by down-regulation of AKT activation. Therefore, blockage of TSPYL5 sensitized A549 cells to cytotoxic agents such as {gamma}-radiation. In addition, TSPYL5 suppression also showed an increased level of p21{sup WAF1/Cip1} and subsequently induced inhibition of cell growth in A549 cells. The overexpression of TSPYL5 in H460 cells showed the opposite effects. This study provides the first demonstration that TSPYL5 modulates cell growth and sensitization of cells to the detrimental effects of damaging agents via regulation of p21{sup WAF1/Cip1} and PTEN/AKT pathway.

• OSTI ID: 22202378
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 392; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOLOGICAL RADIATION EFFECTS
CARCINOMAS
CELL PROLIFERATION
GAMMA RADIATION
GENE REGULATION
INHIBITION
LUNGS
PROTEINS
RNA