Nitrilase 1 modulates lung tumor progression in vitro and in vivo. Oncotarget 2016 Apr 19;7(16):21381-92
Date
03/12/2016Pubmed ID
26967383Pubmed Central ID
PMC5008292DOI
10.18632/oncotarget.7820Scopus ID
2-s2.0-84965043210 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Uncovering novel growth modulators for non-small cell lung cancer (NSCLC) may lead to new therapies for these patients. Previous studies suggest Nit1 suppresses chemically induced carcinogenesis of the foregut in a mouse model. In this study we aimed to determine the role of Nit1 in a transgenic mouse lung cancer model driven by a G12D Kras mutation. Nit1 knockout mice (Nit1-/-) were crossed with KrasG12D/+ mice to investigate whether a G12D Kras mutation and Nit1 inactivation interact to promote or inhibit the development of NSCLC. We found that lung tumorigenesis was suppressed in the Nit1-null background (Nit1-/-:KrasG12D/+). Micro-CT scans and gross tumor measurements demonstrated a 5-fold reduction in total tumor volumes compared to Nit1+/+KrasG12D/+ (p<0.01). Furthermore, we found that Nit1 is highly expressed in human lung cancer tissues and cell lines and use of siRNA against Nit1 decreased overall cell survival of lung cancer cells in culture. In addition, cisplatin response was enhanced in human lung cancer cells when Nit1 was knocked down and Nit1-/-:KrasG12D/+ tumors showed increased sensitivity to cisplatin in vivo. Together, our data indicate that Nit1 may play a supportive role in the modulation of lung tumorigenesis and represent a novel target for NSCLCs treatment.
Author List
Wang YA, Sun Y, Le Blanc JM, Solomides C, Zhan T, Lu BMESH terms used to index this publication - Major topics in bold
A549 CellsAminohydrolases
Animals
Antineoplastic Agents
Blotting, Western
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Cell Survival
Cisplatin
Disease Progression
Humans
Lung Neoplasms
Mice, 129 Strain
Mice, Knockout
Mutation
Proto-Oncogene Proteins p21(ras)
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
