Genomic organization and functional study of a novel tumor suppressor gene - OKL38

Abstract

Cancers are often associated with the mis-regulation of oncogenes and tumour suppressor genes. This thesis illustrates the molecular cloning and characterization of OKL38, a candidate tumour suppressor gene. To further characterize the functions and regulations of OKL38, three novel human and rat OKL38 variants were identified, cloned and characterized. Using the rat model, the regulatory effect of pregnancy and hCG treatment on OKL38 expression in both the rat mammary gland and ovary was determined. Over-expression of OKL38-eGFP recombinant protein in A498, Chang liver and BRL cells lead to protein aggregation and cell death indicating the putative function in regulating cell death. Expression profiling of OKL38 in kidney tumours and HCCs revealed that the lost or reduced expression of OKL38 correlated with high tumour stages in HCC indicating its importance in the progression of kidney and liver cancers. Importantly, deletion study revealed that the 5a?? untranslated region of OKL38 spliced variants played a critical role in regulating translation of its mRNA. A better understanding of the function of OKL38 may lead to the development of new preventative and therapeutic modalities for cancers of the kidney, liver, ovary and breast.