KAI1 tetraspanin and metastasis suppressor.

KAI1 is a widely expressed transmembrane glycoprotein of the tetraspanin family. Substantial experimental evidence suggests that KAI1 is an important regulator of cell behaviour. A loss of KAI1 expression is also associated with the advanced stages of many human malignancies and results in the acquisition of invasive and metastatic capabilities by tumour cells, yet the underlying mechanisms responsible for this down-regulation of KAI1 expression remain to be resolved.

KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells.

A molecular mechanism to explain reduced KAI1 expression in invasive and metastatic tumour cells remains elusive. In this report, we extend an earlier study in bladder cells to confirm that a 76 bp region of the KAI1 promoter (residues -922 to -847), with binding motifs for p53, AP1 and AP2, is required for high level activity of a KAI1 reporter in prostate cancer cell lines. Gel shift and supershift experiments supported binding of p53, junB and heterodimers of AP2alpha/AP2gamma or AP2beta/AP2gamma to this sequence.

Expression and regulation of MIM (Missing In Metastasis), a novel putative metastasis suppressor gene, and MIM-B, in bladder cancer cell lines.

It has been proposed that a 356 amino acid protein encoded by the MIM (Missing In Metastasis) gene on Chromosome 8q24.1, is a bladder cancer metastasis suppressor. Recently, Machesky and colleagues [Biochem.

Methylation of a CpG island within the uroplakin Ib promoter: a possible mechanism for loss of uroplakin Ib expression in bladder carcinoma.

Uroplakin Ib is a structural protein on the surface of urothelial cells. Expression of uroplakin Ib mRNA is reduced or absent in many transitional cell carcinomas (TCCs) but molecular mechanisms underlying loss of expression remain to be determined. Analysis of the uroplakin Ib promoter identified a weak CpG island spanning the proximal promoter, exon 1, and the beginning of intron 1.

Expression of an active p110 catalytic subunit of phosphatidylinositol 3-kinase alters the proliferative capacity of interleukin-2 receptor signals.

Activation of phosphatidylinositol 3-kinase (PI3K) is an early and essential step in interleukin-2 receptor (IL-2R) signalling, and plays an important role in regulating both cell survival and cellular proliferation. In the present study, we utilized Baf-B03 cells expressing mutated IL-2R to examine the contribution of PI3K to proliferative capacity. In this model IL-2-mediated induction of the downstream PI3K-dependent signalling molecule p70 S6 kinase was detected, but there was no proliferative response.

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).