Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss.
Down-regulation of the KAI1 metastasis suppressor gene during the progression of human prostatic cancer infrequently involves gene mutation or allelic loss.
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发表时间：
1996-10
期刊：
影响因子：
11.2
通讯作者：
J. Dong;H. Suzuki;Sokhom S. Pin;G. Bova;J. Schalken;W. Isaacs;Barrett Jc;J. Isaacs
中科院分区：
文献类型：
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作者：
J. Dong;H. Suzuki;Sokhom S. Pin;G. Bova;J. Schalken;W. Isaacs;Barrett Jc;J. Isaacs
KAI1 基因位于人类染色体 11p11.2 上，在某些癌细胞中表达时可抑制肿瘤转移。为了评估 KAI1 失调是否发生在人类前列腺癌的进展过程中，我们使用包含 98 个原发癌和 32 个转移癌的组织库分析了 KAI1 的蛋白表达、突变和等位基因丢失。通过免疫组织化学染色，在正常前列腺和良性前列腺增生组织的上皮细胞而非基质细胞中检测到高水平的 KAI1 蛋白。在上皮细胞中，KAI1 蛋白在质膜上表达。在 49 种未经治疗的原发性前列腺癌患者中，超过 70% 的 KAI1 蛋白表达下调。在 10 名未经治疗的患者中，所有检查的淋巴结转移中都出现了 KAI1 蛋白的下调。在15名雄激素消融治疗失败的转移性疾病患者中，超过90%的原发性前列腺癌出现下调，其中60%没有KAI1蛋白表达。使用源自 KAI1 每个外显子侧翼序列的引物，通过 PLR-单链构象多态性方法分析 KAI1 突变和等位基因丢失。使用这种方法，在 10 名患者的转移瘤中没有检测到点突变或等位基因丢失。通过使用位于 KAI1 区域的标记 D11S1344 进行微卫星分析，在另外 34 个原发灶和 12 个淋巴结转移灶中未检测到等位基因丢失。这些结果表明，KAI1 蛋白表达在人类前列腺癌的进展过程中持续下调，并且这种下调通常不涉及 KAI1 基因的突变或等位基因丢失。
The KAI1 gene, located on human chromosome 11p11.2, suppresses tumor metastasis when expressed in certain cancer cells. To evaluate whether dysregulation of KAI1 occurs during the progression of human prostatic cancer, protein expression, mutation, and allelic loss of KAI1 were analyzed using a tissue bank of 98 primary cancers and 32 metastases. By immunohistochemical staining, high levels of KAI1 protein are detected in the epithelial but not stromal compartment of normal prostatic and benign prostatic hyperplasia tissue. In epithelial cells, KAI1 protein is expressed on the plasma membrane. KAI1 protein expression is downregulated in more than 70% of the 49 primary prostatic cancers from untreated patients. In 10 such untreated patients, down-regulation of KAI1 protein occurred in all of the lymph node metastases examined. In 15 patients with metastatic disease who had failed androgen ablation therapy, more than 90% of the primary prostatic cancers had downregulation, with 60% having no KAI1 protein expression. Primers derived from the sequences flanking each exon of KAI1 were used to analyze KAI1 mutation and allelic loss by the method of PLR-single-strand conformational polymorphism. Using this method, no point mutation or allelic loss was detected in metastases from 10 patients. No allelic loss was detected in an additional 34 primary and 12 lymph node metastases via microsatellite analysis using the marker D11S1344, which is located in the region of KAI1. These results demonstrate that KAI1 protein expression is consistently down-regulated during the progression of human prostatic cancer and that this down-regulation does not commonly involve either mutation or allelic loss of the KAI1 gene.