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.