12p13.1

GPCR5A,PEIG-1,RAI3,RAIG1,TIG1

Breast cancer

Limited studies have shown that human GPRC5A is elevated in human breast cancer specimens and promotes the growth of breast cancer cells.

Lung cancer

GPRC5A is highly expressed in fetal and adult normal lung tissue suggesting that it plays important roles in the embryonic development, maturation and differentiation of these epithelial organs. A study has shown that mice with knockout of both alleles of this gene developed lung adenomas and adenocarcinomas at 12 months onwards at a much higher rate compared to their wild type littermates. The incidence and size of lung tumors was substantially and significantly increased following exposure of Gprc5a knockout mice to the tobacco-specific carcinogen NNK. Moreover, another study derived a gene expression signature from non-malignant lung epithelial Gprc5a knockout and wild type cells and showed that this signature, indicating GPRC5A loss, was associated with poor survival and prognosis in human lung cancer following cross-comparative analysis of human lung cancer microarray datasets. Mechanistically, loss of Gprc5a was shown to induce constitutive activation of the Nf-kB transcriptional factor leading to observed acidic macrophage pneumonia and inflammation in the lung and subsequent increased cellular migration, invasion and oncogenesis. Moreover, loss of Gprc5a was shown to increase JAK/STAT signaling in turn causing elevated cell growth, proliferation and survival. Further, and in accordance with the previous findings of GPRC5A-mediated inhibition of NF-kB, treatment of Gprc5a knockout mice with NTHI increased the severity of observed adenomas implicating inflammation in the course of carcinogenesis downstream of Gprc5a loss.

Non-small cell lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, adenomas.

A gene-expression signature indicating loss of Gprc5A was derived by comparing transcriptome of non-malignant Gprc5a knockout cells compared to wild type cells. This expression signature was found to be highly predictive of poor survival and prognosis in human lung cancer and in particular in human lung adenocarcinomas.

Chronic obstructive pulmonary disease (COPD)

GPRC5A protein, analyzed by immunohistochemical analysis, was shown to be decreased in histologically normal bronchial airway epithelia in COPD patients compared to normal airways from phenotypically normal non-smokers and smokers. Moreover, GPRC5A immunohistochemical protein expression was further decreased in normal bronchial epithelia of patients with both COPD and NSCLC. Given the field cancerization principle and the predisposition of COPD patients to lung cancer, these findings suggest that the GPRC5A protein may be implicated in COPD-associated lung cancer development.

Lung cancer.