Loss of heterozygosity of the PTH/PTHrP type 1 receptor in oral squamous cell carcinoma
Loss of heterozygosity of the PTH/PTHrP type 1 receptor in oral squamous cell carcinoma
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DOI：
10.3892/mmr_00000034
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Kawamura, Hiroshi
中科院分区：
文献类型：
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作者：
Miyashita, Hitoshi;Mori, Shiro;Kawamura, Hiroshi
甲状旁腺激素相关蛋白（Parathyroid hormone-related protein, PTHrP）是各种类型的癌都会产生的，是骨转移发生的重要因素。PTHrP和甲状旁腺激素/甲状旁腺激素相关蛋白1型受体（PTHR1）在癌症中的共表达预示着不良的患者生存。虽然有报道称甲状腺激素受体ss （THRss）的遗传转化与口腔鳞状细胞癌（OSCC）患者的生存率降低有关，但PTHR1基因转化的细节尚未得到广泛分析。本研究的目的是研究OSCC中PTHR1的杂合性缺失（LOH）和微卫星不稳定性（MSI）。显微解剖临床组织基因转化分析显示，PTHR1中LOH和MSI的比例分别为30.0%（3/10）和20.0%（2/10）。此外，p53、FHIT、APC、BRCA1、BRCA2、DCC等抑癌基因在PTHR1染色体上发生LOH而不发生LOH的比例为20.0%（2/10）。这些观察结果表明PTHR1的转化可能参与了人类OSCC的癌变。
Parathyroid hormone-related protein (PTHrP) is produced by various types of carcinomas, and is all important factor in the development of bone metastasis. The coexpression of PTHrP and parathyroid hormone/parathyroid hormone-related protein type 1 receptor (PTHR1) in cancer predicts poor patient survival. While genetic trans formations of thyroid hormone receptor ss (THRss) have been reported as being associated with reduced survival in patients with oral squamous cell carcinoma (OSCC), the details of transformations in PTHR1 have not been extensively analyzed. The aim of this study wits to examine loss of heterozygosity (LOH) and microsatellite instability (MSI) in PTHR1 in OSCC. Analysis of genetic transformations using microdissected clinical tissues revealed that the proportions of LOH and MSI in PTHR1 were 30.0 (3/10) and 20.0% (2/10), respectively. Furthermore, the proportion of carcinomas which developed with LOH on the chromosome of PTHR1 and without LOH for tumor suppressor genes such as p53, FHIT, APC, BRCA1, BRCA2 and DCC was 20.0% (2/10). These observations suggest that transformations in PTHR1 may be involved in carcinogenesis in human OSCC.