Kipl gene expression in neoplasia

The kipl and kip2 proteins have been regarded as potential suppressors of tumorigenicity, by virtue of their ability to regulate the entry of cell into the S-phase through the inhibition of cdk phosphorylation and consequent inhibition of phosphorylation of rb protein. Inevitably therefore there have been some attempts to see if any abnormalities occur in the kip genes in human cancers. These early studies do not suggest the involvement of these genes in the pathogenesis of cancers. Poncecastaneda et al. (1995) investigated a large number of human primary solid tumours and detected no mutations in the kipl gene. Kawamata et al. (1995) also examined a large number of human cancers (432 cases) and cancer cell lines but failed to find any aberrations associated with the kipl gene.

There are a few studies in haemopoietic malignancies which have suggested some alterations in kipl. A non-sense mutation that can result in the production of truncated kipl protein has been reported in codon 76 in one out of 42 cases of adult T-cell leukaemia/ lymphoma (ATL), but is not in matched normal tissue. Some polymorphisms have also been identified in non-Hodgkin's lymphoma. One non-Hodgkin's lymphoma and one ATL showed homozygous deletion of kipl (Morosetti et al, 1995). Loss of heterozygosity has been detected in acute lymphoblastic leukaemia (ALL) but in none of these cases had inactivation of the second allele occurred (Cave et al., 1995). Pietenpol et al. (1995) have also not found any mutations of kipl. It must be recognised, however, that deletions of this region (chromosome 12pl2-13) do occur in leukaemias in a small proportion of childhood ALL and possibly other genes occurring at this location may be involved. The tel gene (an ets family gene coding for transcription factors) is located approximately 1-2 Mbp telomeric from kipl (Sato et al., 1995). Stegmaier et al. (1995) found loss of heterozygosity at the tel gene locus in 15% of informative cases. Allelic loss on chromosome 12, not involving kipl, has been reported also by Takeuchi S et al (1995).

Polymorphisms relating to kipl G A transition at codon 109 in one case and T G transversion in 26% of breast cancer DNA samples and 31 out of 80 normal individuals were detected by Ferrando et al. (1996), but they found no somatic mutations of the gene. These initial studies, albeit a few in number, suggest that kipl alterations may be rare events in the pathogenesis of cancer. There are no studies on the involvement of kip2. But Matsuoka et al. (1995) point out that kip2 region of the human chromosome may be involved in sporadic and with the familial cancer syndrome - the Beckwith-Wiedemann syndrome.

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