Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cell lines and tissues with malignant progression
Isolation and characterization of the major form of human MUC18 cDNA gene and correlation of MUC18 over-expression in prostate cancer cell lines and tissues with malignant progression
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DOI：
10.1016/s0378-1119(01)00736-3
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发表时间：
2001-11-14
期刊：
影响因子：
3.5
通讯作者：
Amin, MB
中科院分区：
文献类型：
--
作者：
Wu, GJ;Wu, MWH;Amin, MB
免疫球蛋白基因超家族中的细胞粘附分子huMUC18的外源性表达可导致非转移性人类黑色素瘤细胞系在裸鼠系统中发生转移。为了确定MUC18的表达是否与前列腺癌的发生和恶性进展相关，我们研究了人MUC18 （huMUC18）在正常前列腺上皮细胞、前列腺癌细胞系、前列腺正常组织和前列腺癌组织中的差异表达。我们克隆并鉴定了人MUC18 (huMUC18) cDNA Cre。从三个人类前列腺癌细胞系和三个人类黑色素瘤细胞系中提取Ne。6个人类癌细胞系的cDNA序列除了1 ~ 5个核苷酸的差异外，其余都是相同的。最长ORF的氨基酸序列为646个氨基酸，除1 ~ 3个氨基酸残基外，其余氨基酸序列完全相同。我们所有的huMUC18 cDNA基因的氨基酸序列除了在相同的7个氨基酸上存在差异外，与其他小组克隆的氨基酸序列相似（GenBank访问#M28882）。我们认为，本文报道的huMUC18 cDNA基因代表了一个主要等位基因的基因产物。MUC18 mRNA和蛋白在3种转移性前列腺癌细胞系（TSU-PR1、DU145和PC-3）中表达，而在1种非转移性前列腺癌细胞系（LNCaP.FGC）中不表达。在这四种细胞系中，huMUC18的表达与其在裸鼠体内的移动性、侵袭性和体内转移程度呈正相关。在含有高级别前列腺上皮内瘤变（PIN）的组织样本切片中制备的提取物中，HuMUC18蛋白也有高水平表达，但在培养的原代正常前列腺上皮细胞和正常前列腺中制备的提取物中表达较弱。免疫组织化学分析显示，与正常或良性增生性上皮（BPH）相比，huMUC18在高级别PIN和前列腺癌的上皮细胞、神经周围浸润细胞、淋巴结和肺转移细胞中的表达水平更高。因此，我们得出结论，MUC18的表达在前列腺癌起始（高级别PIN）和癌进展过程中，以及在转移细胞系和转移癌中增加。MUC18的表达增加在人类前列腺癌的发生和恶性进展中起重要作用。此外，缺乏MUC18的主要细胞质膜表达似乎与前列腺癌的恶性进展有关。(C) 2001 Elsevier Science B.V.版权所有
Ectopical expression of huMUC18, a cell adhesion molecule in the immunoglobulin gene superfamily, causes a non-metastatic human melanoma cell line to become metastatic in a nude mouse system. To determine if MUC18 expression correlates with the development and malignant progression of prostate cancer, we investigated differential expression of human MUC18 (huMUC18) in normal prostate epithelial cells, prostate cancer cell lines, and prostatic normal and cancer tissues. We cloned and characterized the human MUC18 (huMUC18) cDNA Cre. ne from three human prostate cancer cell lines and three human melanoma cell lines. The cDNA sequences from the six human cancer cell lines were identical except differences in one to five nucleotides. The deduced amino acid sequences of the longest ORF were 646 amino acids that were identical in these cDNAs except for one to three amino acid residues. The amino acid sequences of all our huMUC18 cDNA genes are similar to that cloned by other group (GenBank access #M28882) except differences in the same seven amino acids. We conclude that huMUC18 cDNA gene reported here represents the gene product from a major allele. The MUC18 mRNA and protein was expressed in three metastatic prostate cancer cell lines (TSU-PR1, DU145, and PC-3), but not in one non-metastatic prostate cancer cell line (LNCaP.FGC). The expression of huMUC18 in these four cell lines is positively related to their extent of in vitro motility and invasiveness and in vivo metastasis in nude mice. HuMUC18 protein was also expressed at high levels in extracts prepared from tissue sample sections containing high grade prostatic intraepithelial neoplasia (PIN), but weakly expressed in extracts prepared from cultured primary normal prostatic epithelial cells and the normal prostate gland. Immunohistochemical analysis showed that huMUC18 was expressed at higher levels in the epithelial cells of high-grade PIN and prostatic carcinomas, and in cells of a perineural invasion, a lymph node, and a lung metastases compared to that in normal or benign hyperplastic epithelium (BPH). We therefore conclude that MUC18 expression is increased during prostate cancer initiation (high grade PIN) and progression to carcinoma, and in metastatic cell lines and metastatic carcinoma. Increased expression of MUC18 is implicated to play an important role in developing and malignant progression of human prostate cancer. Furthermore, the lacking of predominant cytoplasmic membrane expression of MUC18 appeared to correlate with malignant progression of prostate cancer. (C) 2001 Elsevier Science B.V. All rights reserved.