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Repression of G protein–coupled receptor family C group 5 member A is associated with pathologic differentiation grade of oral squamous cell carcinoma
Authors:Shu‐li Liu  Shuang‐shuang Zhong  Dong‐xia Ye  Wan‐tao Chen  Zhi‐yuan Zhang  Jiong Deng
Affiliation:1. Department of Oral and Maxillofacial–Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, , Shanghai, China;2. Key laboratory of cell differentiation and apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, , Shanghai, China;3. Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, , Shanghai, China
Abstract:

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.
Keywords:GPRC5A  immunohistochemistry  oral squamous cell carcinoma
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