Repression of G protein-coupled receptor family C group 5 member A is associated with pathologic differentiation grade of oral squamous cell carcinoma
Repression of G protein-coupled receptor family C group 5 member A is associated with pathologic differentiation grade of oral squamous cell carcinoma
复制标题
G蛋白偶联受体家族C组5成员A的抑制与口腔鳞状细胞癌的病理分化级别相关。
DOI：
10.1111/jop.12077
复制
发表时间：
2013-11-01
影响因子：
3.3
通讯作者：
Deng, Jiong
中科院分区：
文献类型：
--
作者：
Liu, Shu-li;Zhong, Shuang-shuang;Deng, Jiong
背景
G蛋白偶联受体家族C组5成员A（GPRC5A）是G蛋白偶联受体家族的成员，在肺组织中具有肿瘤抑制作用。因此，GPRC5A的生物学功能与肺组织有关。然而，这种基因产物的生物学意义仍然模糊不清。在这项研究中，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细胞系中表征其生物学活性。
方法
采用免疫印迹法和免疫组化法检测GPRC5A在口腔鳞癌细胞系和临床标本中的表达。GPRC5A稳定转染子及其亲本OSCC细胞的特征在于其在锚定非依赖性生长中的生物活性。
结果
GPRC5A在正常口腔黏膜组织中呈高表达，尤其是分化区。与此相反，GPRC5A在OSCC中的表达显著受抑制（P < 0.01）。免疫组化GPRC5A的表达是中等分化，但在中等分化的OSCC中受到很大抑制，在低分化的OSCC中完全抑制。GPRC5A在OSCC CAL 27细胞中的过表达导致了抑制的锚定非依赖性生长活性，即转化表型。
结论
GPRC5A在正常口腔上皮中表达。GPRC5A的抑制与OSCC的差分化等级相关。GPRC5A过表达可逆转OSCC细胞的恶性表型。因此，GPRC5A在口腔组织中的稳态是重要的，并且该基因的缺失或抑制可能参与OSCC的肿瘤发生，并且可以作为恶性类型OSCC的预后标志物。
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.