Other
12 Authors
- Lotan R,
- Lacroix L,
- Fujimoto J,
- Tao Q,
- Mao L,
- Lee JJ,
- Deng J,
- Men T,
- Lotan D,
- Clifford JL,
- Ye X,
- Van Pelt CS
| First Author | Tao Q | Year | 2007 |
| Journal | J Natl Cancer Inst | Volume | 99 |
| Issue | 22 | Pages | 1668-82 |
| PubMed ID | 18000218 | Mgi Jnum | J:127821 |
| Mgi Id | MGI:3765112 | Doi | 10.1093/jnci/djm208 |
| Citation | Tao Q, et al. (2007) Identification of the retinoic acid-inducible Gprc5a as a new lung tumor suppressor gene. J Natl Cancer Inst 99(22):1668-82 |
| abstractText | BACKGROUND: Lung cancers develop via multiple genetic and epigenetic changes, including inactivation of tumor suppressor genes. We previously cloned human G protein-coupled receptor family C type 5A (GPRC5A), whose expression is suppressed in some human lung carcinoma cells, and its mouse homolog Gprc5a. METHODS: We generated Gprc5a knockout mice by homologous recombination and studied their phenotype by macroscopic observation and microscopic histologic analysis of embryos and lungs of 1- to 2-year-old mice. GPRC5A mRNA expression was analyzed by reverse transcription-polymerase chain reaction in surgical specimens of 18 human lung tumors and adjacent normal tissues and by analyzing previously published data from 186 lung tumor tissues of a variety of histologic types and 17 normal lung samples. Human embryonic kidney, human non-small-cell lung cancer, and mouse lung adenocarcinoma cells were transfected with a GPRC5A expression vector or a control vector, and colony formation in semisolid medium was assayed. Statistical tests were two-sided. RESULTS: Homozygous knockout mice developed many more lung tumors at 1-2 years of age (incidence: 76% adenomas and 17% adenocarcinomas) than heterozygous (11% adenomas) or wild-type (10% adenomas) mice. Human GPRC5A mRNA levels were lower in most (11 of 18 [61%]) human lung tumors than in adjacent normal tissues. The mean GPRC5A mRNA level in adenocarcinoma (n = 139), squamous cell carcinoma (n = 21), small-cell lung cancer (n = 6), and carcinoid (n = 20) tissues was 46.2% (P = .014), 7.5% (P<.001), 5.3% (P<.001), and 1.8% (P<.001), respectively, that in normal lung tissues (n = 17) GPRC5A transfection suppressed colony formation in semisolid medium of immortalized human embryonic kidney, human non-small-cell lung cancer, and mouse lung adenocarcinoma cells by 91%, 91%, and 68%, respectively, compared with vector controls (all P<.001). CONCLUSIONS: Gprc5a functions as a tumor suppressor in mouse lung, and human GPRC5A may share this property. The Gprc5a-deficient mouse is a novel model to study lung carcinogenesis and chemoprevention. |
