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多形性腺瘤恶变过程中HIF-1α、GLUT-1、FASN和脂联素的基因及免疫组化表达

Gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in carcinoma ex pleomorphic adenoma development.

作者信息

Scarini João Figueira, Rosa Larissa Fernandes, Souza Reydson Alcides de Lima, Egal Erika Said Abu, Tincani Alfio José, Martins Antônio Santos, Kowalski Luiz Paulo, Graner Edgard, Coletta Ricardo Della, Carlos Roman, Gondak Rogério de Oliveira, de Almeida Oslei Paes, Altemani Albina Messias de Almeida Milani, Bastos Débora Campanella, Mariano Fernanda Viviane

机构信息

Oral Diagnosis Department, Piracicaba Dental School/UNICAMP, Piracicaba, Brazil.

Pathology Department, Faculty of Medical Sciences/UNICAMP, Campinas, Brazil.

出版信息

Oral Dis. 2020 Sep;26(6):1190-1199. doi: 10.1111/odi.13332. Epub 2020 Apr 2.

DOI:10.1111/odi.13332
PMID:32180291
Abstract

OBJECTIVE

To analyze the gene and immunohistochemical expression of HIF-1α, GLUT-1, FASN, and adipophilin in normal salivary gland (NSG), pleomorphic adenoma (PA), and carcinoma ex pleomorphic adenoma (CXPA) samples.

MATERIAL AND METHODS

The gene expression was investigated by the real-time PCR (qRT-PCR) method in 9 samples of frozen tissues of normal salivary gland, 13 PA, and 10 CXPA. We validated the reactions by immunohistochemistry on 20 samples from NSG, 85 PA, and 44 CXPA.

RESULTS

Our results showed that there was no statistically significant difference in HIF-1α gene and immunohistochemistry expression among the tissues studied while FASN gene and immunohistochemistry expression increased along the carcinogenesis of the PA. GLUT-1 was significantly more expressed in tumor tissues (PA and CXPA), although protein is mainly expressed in transformed cells than in PA and NSG. In contrast, adipophilin was significantly more expressed in NSG while the expression of the protein increased in PA and CXPA.

CONCLUSIONS

In summary, the data presented here suggest that neoplastic cells reprogram the expression of GLUT-1 and adipophilin to adapt to the tumor microenvironment and reinforce, through immunohistochemical results, a possible transcriptional and post-translational regulatory mechanisms that act on the expression of these genes.

摘要

目的

分析正常涎腺(NSG)、多形性腺瘤(PA)及多形性腺瘤恶变(CXPA)样本中低氧诱导因子-1α(HIF-1α)、葡萄糖转运蛋白1(GLUT-1)、脂肪酸合酶(FASN)和脂联素的基因及免疫组化表达情况。

材料与方法

采用实时荧光定量聚合酶链反应(qRT-PCR)法检测9例正常涎腺冷冻组织样本、13例多形性腺瘤样本及10例多形性腺瘤恶变样本中的基因表达情况。通过免疫组化对20例正常涎腺样本、85例多形性腺瘤样本及44例多形性腺瘤恶变样本进行验证。

结果

结果显示,在所研究的组织中,HIF-1α基因及免疫组化表达无统计学显著差异,而FASN基因及免疫组化表达随多形性腺瘤的癌变过程而增加。葡萄糖转运蛋白1在肿瘤组织(多形性腺瘤和多形性腺瘤恶变)中表达显著更高,尽管其蛋白主要在转化细胞中表达,而非在多形性腺瘤和正常涎腺中。相反,脂联素在正常涎腺中表达显著更高,而其蛋白表达在多形性腺瘤和多形性腺瘤恶变中增加。

结论

总之,本文数据表明,肿瘤细胞重新编程葡萄糖转运蛋白1和脂联素的表达以适应肿瘤微环境,并通过免疫组化结果强化了一种可能作用于这些基因表达的转录和翻译后调控机制。

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