DOWN-REGULATION OF THE KAI1 METASTASIS SUPPRESSOR GENE DURING THE PROGRESSION OF HUMAN PROSTATIC-CANCER INFREQUENTLY INVOLVES GENE MUTATIONOR ALLELIC LOSS

The KAI1 gene, located on human chromosome 11p11.2, suppresses tumor m etastasis 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 a nalyzed using a tissue bank of 98 primary cancers and 32 metastases. B y immunohistochemical staining, high levels of KAI1 protein are detect ed in the epithelial but not stromal compartment of normal prostatic a nd benign prostatic hyperplasia tissue. In epithelial cells, KAI1 prot ein is expressed on the plasma membrane. KAI1 protein expression is do wnregulated 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 downregula tion, with 60% having no KAI1 protein expression. Primers derived from the sequences flanking each exon of KAI1 were used to analyze KAI1 mu tation and allelic loss by the method of PCR-single-strand conformatio nal polymorphism. Using this method, no point mutation or allelic loss was detected in metastases from 10 patients. No allelic loss was dete cted in an additional 34 primary and 12 lymph node metastases via micr osatellite analysis using the marker D11S1344, which is located in the region of KAI1. These results demonstrate that KAI1 protein expressio n is consistently down-regulated during the progression of human prost atic cancer and that this down-regulation does not commonly involve ei ther mutation or allelic loss of the KAI1 gene.