Bouras T, Frauman A G
Molecular Immunology Laboratory, Clinical Pharmacology and Therapeutics Unit, The University of Melbourne, Department of Medicine, Austin and Repatriation Medical Centre, Austin Campus, Heidelberg, Victoria 3084, Australia.
J Pathol. 1999 Aug;188(4):382-8. doi: 10.1002/(SICI)1096-9896(199908)188:4<382::AID-PATH365>3.0.CO;2-O.
The KAI1 gene, isolated from human chromosome 11p11.2, has been implicated as a prostate cancer metastasis suppressor gene. Recent studies have demonstrated that the expression of KAI1 protein is reduced in metastases of human prostate cancers and is inversely correlated with tumour grade. The objectives of the present work were to determine whether alterations of KAI1 at a genetic level in localized prostate cancers correlate with degrees of differentiation. This paper reports the application of semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Southern analysis to two different regions of the KAI1 gene on 35 microdissected primary prostate cancer specimens and demonstrates a biphasic pattern of KAI1 expression according to histological grade. KAI1 mRNA, relative to the housekeeping gene beta -actin, was elevated in low-grade primary prostate cancer (2.7+/-0.4) compared with non-malignant (hyperplastic) prostatic tisues (0.92+/-0.02, p< 0.05), yet reduced in high-grade primary cancers (0.61+/-0.11, p< 0. 05). These data demonstrate, for the first time, that KAI1 is biphasically expressed in primary prostate cancers and suggest that hyperexpression of KAI1 in low-grade prostate cancer may be associated with restraint of tumour progression, whereas a relative decrease in KAI1 gene expression may accompany more aggressive cancers through loss of such restraint. This differential expression of the metastasis suppressor gene KAI1 in primary prostate cancers may have important prognostic implications for the development of subsequent metastases. Should the level of KAI1 in primary prostate cancer be correlated with patient outcome such information may, in the future, enable more intensive adjuvant therapy to be directed to those patients identified to be at greatest risk of metastasis.
从人染色体11p11.2分离出的KAI1基因，被认为是一种前列腺癌转移抑制基因。最近的研究表明，KAI1蛋白的表达在人前列腺癌转移灶中降低，且与肿瘤分级呈负相关。本研究的目的是确定局限性前列腺癌中KAI1基因水平的改变是否与分化程度相关。本文报道了对35个经显微切割的原发性前列腺癌标本的KAI1基因两个不同区域应用半定量逆转录-聚合酶链反应（RT-PCR）和Southern分析，并根据组织学分级展示了KAI1表达的双相模式。相对于管家基因β-肌动蛋白，KAI1 mRNA在低级别原发性前列腺癌中升高（2.7±0.4），与非恶性（增生性）前列腺组织（0.92±0.02，p<0.05）相比，但在高级别原发性癌症中降低（0.61±0.11，p<0.05）。这些数据首次证明，KAI1在原发性前列腺癌中呈双相表达，并表明KAI1在低级别前列腺癌中的高表达可能与肿瘤进展的抑制有关，而KAI1基因表达的相对降低可能伴随着更具侵袭性的癌症，因为这种抑制作用丧失。转移抑制基因KAI1在原发性前列腺癌中的这种差异表达可能对后续转移的发生具有重要的预后意义。如果原发性前列腺癌中KAI1的水平与患者预后相关，那么此类信息未来可能使更强化的辅助治疗能够针对那些被确定为转移风险最高的患者。
