Abstract：
OBJECTIVE: Pleomorphic adenoma (PA), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) are the most prevalent salivary gland tumors. Their pathogenesis has been recently associated with complex molecular cascades, including the TGFβ signaling pathway. The aim of this study was to evaluate the expression of genes associated with the TGFβ signaling pathway (TGFB1, ITGB6, SMAD2, SMAD4, FBN1, LTBP1, and c-MYC) to map possible downstream alterations in the TGFβ cascade.
METHODS: Thirteen PA, 17 MEC, 13 ACC, and 10 non-neoplastic salivary gland samples were analyzed by real-time RT-PCR.
RESULTS: Cases of PA presented increased TGFB1, LTPB1, c-MYC, and FBN1 expressions, whereas SMAD2 expression was decreased when compared to non-neoplastic tissue. MEC patients displayed increased expressions of TGFB1, ITGB6, FBN1, and c-MYC and decreased expressions of SMAD2 and SMAD4. ACC cases exhibited elevated expressions of the investigated genes except TGFB1. The present results suggest that decreased expression of SMAD2 and SMAD4 does not impede the transcriptional regulation of c-MYC, especially in PA and MEC. Increased expressions of ITGB6, TGFB1, LTBP1, and FBN1 appear to be related to the regulation of the TGFβ signaling pathway in these tumors. Additionally, we observed a higher expression of SMAD4 in ACC and a raised expression of ITGB6 and lowered expression of SMAD2 in MEC.
CONCLUSIONS: Our study demonstrated the differential expression of TGFβ cascade members in salivary gland tumors such as SMAD2/SMAD4 and c-MYC as well as the participation of ITGB6, TGFB1, LTBP1, and FBN1, contributing to the understanding of the mechanisms involved in tumor progression.
METHODS: Thirteen PA, 17 MEC, 13 ACC, and 10 non-neoplastic salivary gland samples were analyzed by real-time RT-PCR.
RESULTS: Cases of PA presented increased TGFB1, LTPB1, c-MYC, and FBN1 expressions, whereas SMAD2 expression was decreased when compared to non-neoplastic tissue. MEC patients displayed increased expressions of TGFB1, ITGB6, FBN1, and c-MYC and decreased expressions of SMAD2 and SMAD4. ACC cases exhibited elevated expressions of the investigated genes except TGFB1. The present results suggest that decreased expression of SMAD2 and SMAD4 does not impede the transcriptional regulation of c-MYC, especially in PA and MEC. Increased expressions of ITGB6, TGFB1, LTBP1, and FBN1 appear to be related to the regulation of the TGFβ signaling pathway in these tumors. Additionally, we observed a higher expression of SMAD4 in ACC and a raised expression of ITGB6 and lowered expression of SMAD2 in MEC.
CONCLUSIONS: Our study demonstrated the differential expression of TGFβ cascade members in salivary gland tumors such as SMAD2/SMAD4 and c-MYC as well as the participation of ITGB6, TGFB1, LTBP1, and FBN1, contributing to the understanding of the mechanisms involved in tumor progression.
摘要：
目标：多形性腺瘤（PA），粘液表皮样癌（MEC），腺样囊性癌（ACC）是最常见的唾液腺肿瘤。它们的发病机制最近与复杂的分子级联反应有关，包括TGFβ信号通路。这项研究的目的是评估与TGFβ信号通路相关的基因（TGFB1，ITGB6，SMAD2，SMAD4，FBN1，LTBP1和c-MYC）的表达，以定位TGFβ级联中可能的下游改变。
方法：十三PA，17MEC，13ACC,通过实时RT-PCR分析了10例非肿瘤性唾液腺样品。
结果：PA病例显示TGFB1、LTPB1、c-MYC升高，和FBN1表达式，而与非肿瘤组织相比，SMAD2表达降低。MEC患者显示TGFB1，ITGB6，FBN1和c-MYC的表达增加，SMAD2和SMAD4的表达降低。ACC病例除TGFB1外，所研究基因的表达均升高。目前的结果表明，SMAD2和SMAD4的表达降低并不妨碍c-MYC的转录调控。尤其是PA和MEC。在这些肿瘤中，ITGB6，TGFB1，LTBP1和FBN1的表达增加似乎与TGFβ信号通路的调节有关。此外,我们观察到ACC中SMAD4的表达更高，MEC中ITGB6的表达升高和SMAD2的表达降低。
结论：我们的研究表明TGFβ级联成员在唾液腺肿瘤如SMAD2/SMAD4和c-MYC中的差异表达，以及ITGB6、TGFB1、LTBP1和FBN1的参与，有助于理解肿瘤进展的机制。
方法：十三PA，17MEC，13ACC,通过实时RT-PCR分析了10例非肿瘤性唾液腺样品。
结果：PA病例显示TGFB1、LTPB1、c-MYC升高，和FBN1表达式，而与非肿瘤组织相比，SMAD2表达降低。MEC患者显示TGFB1，ITGB6，FBN1和c-MYC的表达增加，SMAD2和SMAD4的表达降低。ACC病例除TGFB1外，所研究基因的表达均升高。目前的结果表明，SMAD2和SMAD4的表达降低并不妨碍c-MYC的转录调控。尤其是PA和MEC。在这些肿瘤中，ITGB6，TGFB1，LTBP1和FBN1的表达增加似乎与TGFβ信号通路的调节有关。此外,我们观察到ACC中SMAD4的表达更高，MEC中ITGB6的表达升高和SMAD2的表达降低。
结论：我们的研究表明TGFβ级联成员在唾液腺肿瘤如SMAD2/SMAD4和c-MYC中的差异表达，以及ITGB6、TGFB1、LTBP1和FBN1的参与，有助于理解肿瘤进展的机制。
