Liu Shu-li, Zhong Shuang-shuang, Ye Dong-xia, Chen Wan-tao, Zhang Zhi-yuan, Deng Jiong
Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
J Oral Pathol Med. 2013 Nov;42(10):761-8. doi: 10.1111/jop.12077. Epub 2013 May 7.
G protein-coupled receptor family C group 5 member A (GPRC5A), a member of G protein-coupled receptor family, has been shown to function as a tumor suppressor in lung tissue. The biological functions of GPRC5A have therefore been linked to lung tissue. However, the biological significance of this gene product remains obscure. In this study, we investigated the expression of GPRC5A proteins in normal oral tissue and oral squamous cell carcinoma (OSCC), and we characterized its biological activity in OSCC cell lines.
Western blot analysis and immunohistochemical staining were used to investigate the expression of GPRC5A in both OSCC cell lines and clinical samples. GPRC5A stable transfectants and their parental OSCC cells were characterized for their biological activities in anchorage-independent growth.
High levels of immunohistochemical GPRC5A expression were detected in normal oral tissue, especially differentiated area. In contrast, GPRC5A expression was dramatically repressed in OSCCs (P < 0.01). The immunohistochemical GPRC5A expression was moderately well differentiated, but greatly repressed in moderately differentiated OSCCs and completely repressed in poorly differentiated OSCCs. Overexpression of GPRC5A in OSCC CAL27 cells resulted in a suppressed anchorage-independent growth activity, a transforming phenotype.
GPRC5A is expressed in normal oral epithelium. Repression of GPRC5A is associated with poorly differential grade of OSCCs. Overexpression of GPRC5A in OSCC cell line reversed the malignant phenotype. Thus, GPRC5A is important for homeostasis in oral tissue, and deletion or repression of this gene may involve in tumorigenesis of OSCCs and may serve as a prognostic marker for malignant type of OSCCs.
G蛋白偶联受体C类第5组成员A（GPRC5A）是G蛋白偶联受体家族的成员之一，已被证明在肺组织中发挥肿瘤抑制作用。因此，GPRC5A的生物学功能与肺组织相关。然而，这种基因产物的生物学意义仍不清楚。在本研究中，我们调查了GPRC5A蛋白在正常口腔组织和口腔鳞状细胞癌（OSCC）中的表达，并在OSCC细胞系中表征了其生物学活性。
采用蛋白质印迹分析和免疫组织化学染色法研究GPRC5A在OSCC细胞系和临床样本中的表达。对GPRC5A稳定转染子及其亲本OSCC细胞进行非锚定依赖性生长的生物学活性表征。
在正常口腔组织，尤其是分化区域检测到高水平的免疫组织化学GPRC5A表达。相比之下，GPRC5A在OSCC中的表达显著下调（P < 0.01）。免疫组织化学GPRC5A表达在中度分化的OSCC中中等程度下调，但在中度分化的OSCC中显著下调，在低分化的OSCC中完全下调。GPRC5A在OSCC CAL27细胞中的过表达导致非锚定依赖性生长活性受到抑制，这是一种转化表型。
GPRC5A在正常口腔上皮中表达。GPRC5A的抑制与OSCC的低分化程度相关。GPRC5A在OSCC细胞系中的过表达逆转了恶性表型。因此，GPRC5A对口腔组织的稳态很重要，该基因的缺失或抑制可能参与OSCC的肿瘤发生，并可能作为OSCC恶性类型的预后标志物。
