Identification of regulatory regions within the KAI1 promoter: a role for binding of AP1, AP2 and p53.

The mechanism underlying loss of KAI1 gene expression in invasive and metastatic tumour cells is unknown. A possible scenario could involve altered expression or function of protein factors normally involved in regulating KAI1 transcription. To explore this possibility, we have initiated a study to characterise regulatory elements of the KAI1 promoter, using as a model, two bladder cancer cell lines (BL13 and HT1376) expressing high levels of endogenous KAI1 messenger RNA (mRNA).

Relationship between expression of KAI1 metastasis suppressor gene, mRNA levels and p53 in human bladder and prostate cancer cell lines.

The molecular basis for the loss of KAI1 expression in invasive and metastatic tumors and tumor cell lines is not understood. Recently, identification of a sequence with homology to the consensus p53-binding motif in the promoter of the KAI1 metastasis suppressor gene, has led to a proposal that transcriptional regulation by p53 controls expression of KAI1, and that a dramatic down-regulation of KAI1 mRNA levels in invasive tumors and many tumor cell lines, is directly due to loss of p53 function. We have tested this hypothesis by assessing KAI1 mRNA levels in a series of 22 cell lines derived from bladder and prostate cancers, in which we confirmed the p53 gene sequence and characterized the functional status of the endogenous p53 protein.