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.