Yonezawa Suguru, Goto Masamichi, Yamada Norishige, Higashi Michiyo, Nomoto Mitsuharu
Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Proteomics. 2008 Aug;8(16):3329-41. doi: 10.1002/pmic.200800040.
Mucins are high molecular weight glycoproteins that play important roles in carcinogenesis or tumor invasion. To clarify the relationship of the expression patterns of mucins in human neoplasms with their biological behavior, we examined the expression profiles of MUC1, MUC2, and MUC4 mucins in various human neoplasms using immunohistochemistry and in situ hybridization, and compared them with clinicopathologic factors including outcome of the patients. MUC1 or MUC4 expression is related with the aggressive behavior of human neoplasms and a poor outcome of the patients. In contrast, MUC2 expression tends to be related with the indolent behavior of human neoplasms and a favorable outcome of the patients, although indolent pancreatobiliary neoplasms sometimes show invasive growth with MUC1 expression in the invasive areas. The expression of MUC2 mucin in indolent pancreatobiliary neoplasms coincided with expression of MUC2 mRNA. Our recent studies to clarify the MUC2 gene regulation mechanism disclosed that DNA methylation and histone modification in the 5' flanking region of the MUC2 promoter may play an important role. Further studies of the epigenetics also in MUC1 and MUC4 gene expression may be needed to understand the relationship between the expression of mucins in human neoplasms with their biological behavior.
黏蛋白是高分子量糖蛋白，在肿瘤发生或肿瘤侵袭中起重要作用。为了阐明人类肿瘤中黏蛋白的表达模式与其生物学行为之间的关系，我们使用免疫组织化学和原位杂交技术检测了多种人类肿瘤中MUC1、MUC2和MUC4黏蛋白的表达谱，并将其与包括患者预后在内的临床病理因素进行了比较。MUC1或MUC4的表达与人类肿瘤的侵袭性行为及患者的不良预后相关。相比之下，MUC2的表达往往与人类肿瘤的惰性生物学行为及患者的良好预后相关，尽管惰性胰胆肿瘤有时在侵袭区域会出现伴有MUC1表达的侵袭性生长。惰性胰胆肿瘤中MUC2黏蛋白的表达与MUC2 mRNA的表达一致。我们最近旨在阐明MUC2基因调控机制的研究表明，MUC2启动子5'侧翼区域的DNA甲基化和组蛋白修饰可能起重要作用。可能还需要进一步研究MUC1和MUC4基因表达中的表观遗传学，以了解人类肿瘤中黏蛋白的表达与其生物学行为之间的关系。
