Ermak G, Jennings T, Boguniewicz A, Figge J
Departments of Medicine and Pathology, Albany Medical College, Albany, New York 12208, USA.
Clin Cancer Res. 1996 Aug;2(8):1251-4.
CD44 is a family of cell surface proteins implicated in adhesion interactions and tumor metastasis. Multiple CD44 mRNA isoforms arise from alternative splicing of variant exons (termed v1-v10). We recently discovered a novel CD44 mRNA isoform in human papillary thyroid cancers featuring a junction between subsegments of exons 4 and 13 (v8). The sequence ACAG was repeated at both the donor and acceptor sites in the genomic DNA (G. Ermak et al., Cancer Res., 56: 1037-1042, 1996). We used reverse transcription-PCR to characterize expression of this isoform in a panel of thyroid lesions. In addition, we assayed three cryopreserved human breast cancers and two samples of normal breast tissue (from female subjects who had undergone cosmetic mammoplasty) to determine whether a similar isoform is present in breast carcinomas. Levels of the novel isoform were up-regulated in 88% of the goiters, adenomas, and papillary cancers, but were undetectable in cases of thyroiditis and absent or low-level in four samples of normal thyroid tissue. The three breast cancers each yielded a 546-bp PCR product that was not detected in normal breast tissue. The PCR product from one of the breast cancers was cloned, and sequence analysis revealed a novel mRNA isoform featuring a junction between exon 3 and an internal site within exon 13 (v8). The sequence GCTTCAG was repeated at both the donor and acceptor sites in the genomic DNA. These results show that human thyroid and breast tissues contain novel CD44 mRNA isoforms featuring unusual rearrangements at repeated sequences. Further studies are warranted to determine whether the expression of this class of isoforms correlates with growth status.
CD44是一族参与黏附相互作用和肿瘤转移的细胞表面蛋白。多种CD44 mRNA异构体源于可变外显子（称为v1 - v10）的可变剪接。我们最近在人甲状腺乳头状癌中发现了一种新的CD44 mRNA异构体，其特征是外显子4和13（v8）的亚段之间存在连接。基因组DNA的供体和受体位点均重复出现序列ACAG（G. Ermak等人，《癌症研究》，56: 1037 - 1042，1996）。我们使用逆转录 - PCR来表征该异构体在一组甲状腺病变中的表达。此外，我们检测了三个冷冻保存的人乳腺癌样本和两个正常乳腺组织样本（来自接受美容性乳房成形术的女性受试者），以确定乳腺癌中是否存在类似的异构体。在88%的甲状腺肿、腺瘤和乳头状癌中，新异构体的水平上调，但在甲状腺炎病例中未检测到，并且在四个正常甲状腺组织样本中不存在或水平较低。三个乳腺癌样本均产生了一个546 bp的PCR产物，而在正常乳腺组织中未检测到。其中一个乳腺癌样本的PCR产物被克隆，序列分析揭示了一种新的mRNA异构体，其特征是外显子3与外显子13内的一个内部位点（v8）之间存在连接。基因组DNA的供体和受体位点均重复出现序列GCTTCAG。这些结果表明，人甲状腺和乳腺组织含有具有重复序列处异常重排特征的新型CD44 mRNA异构体。有必要进行进一步研究以确定这类异构体的表达是否与生长状态相关。
