Mice lacking GPRC5A were more likely to develop cancer, according to study in JNCI.
The GPRC5A gene suppresses lung tumors in mouse models, according to researchers at The University of Texas M. D. Anderson Cancer Center.
The study found that mice with both their GPRC5A genes suppressed developed normally until their second year of life, when 76% developed precancerous lesions called adenomas in their lungs and another 17% developed adenocarcinomas. Additionally, 10% of mice with both GPRC5A genes intact and 11% with one working version of the gene developed adenomas. None of the mice in the latter two groups developed lung cancer.
The team also discovered that the tumors generated in the mice without the genes lacked mutations to the K-Ras gene, a common oncogene that fuels cancer growth.
The investigators then compared expression of the gene in 18 pairs of human non-small-cell lung cancer and adjacent normal tissue. In 61% of the cases, the tumors had lower levels of GPRC5A mRNA than did the nearby normal tissue. Two had higher levels of expression in the tumor and one pair had similar levels in both tissues. Four had no expression in either sample.
Next, the team compared 186 lung tumors to 17 normal control tissues. The four tumor types all had a fraction of the GPRC5A gene expression shown in the normal cells: adenocarcinoma 46.2%; squamous cell carcinoma at 7.5%; small-cell lung cancer at 5.3%; and carcinoid at 1.8%.
Finally, when they inserted the GPRC5A gene back into lung cancer cell lines, colony formation of human lung cancer cells was suppressed by 91% in two cell lines.
The study is published online in the Journal of the National Cancer Institute.