ESTIMATION OF HOMOZYGOTE RECESSIVE AND HETEROZYGOUS CDK3 DISTRIBUTION IN RANDOMLY SELECTED CANCER SUBJECTS

Abstract

Cdk3 is well known cell regulating protein and has prominence role in cancer development. Studies relating to different phenotypes in various cancers would estimate the frequency of distribution among Indian patients suffering from cancer. Such distribution of Cdk3 was found to be 55.5% in coastal Andhra which is homozygote recessive and 44.4% being heterozygous. KEY WORDS: Cdk (Cyclin-dependent kinase), Cell regulating protein, Polymorphism and SNP (Single Nucleotide Polymorphism). INTRODUCTION: Cyclin-dependent kinases (cdk) are serine/threonine protein kinases that play essential roles in the control of cell cycle progression by interacting with a variety of regulators and substrates. In the mammalian cell cycle, the transition from the Go/G1 phase to S phase, in which DNA replication occurs, has been shown to be regulated by cyclin-dependent kinases (cdks). Activities of cdks are controlled by association with cyclins and reversible phosphorylation reactions. An additional level of regulation is provided by inhibitors of cdks. Two families of these inhibitors have been described, those that interact with a wide range of cyclin/cdk complexes, including p21, p27 and p57, and those that only inhibit cdk4 and cdk6, including p15, p16, p18 and p19 [1]. In eukaryotic cells, cell cycle progression is driven by the sequential and periodic activation of cyclin/cdks, and dysregulation of the cell cycle is associated with cancer development [2-4]. Over expression of cdk6 has been observed in lymphomas, leukemias, and melanomas due to chromosomal translocation [5, 6]. Cdks are closely associated with human cancer pathogenesis. Cdk3 is an important regulator of cell cycle. The activity of cdk3 is first observed in early G1 phase [16] and reaches a peak in mid-G1 [7]. A dominant-negative cdk3 was shown to induce G1 arrest, which could not be rescued by cdk2, indicating that cdk3 plays an important role for G1 exit to S entry [8-9]. Recently, cdk3 was found to form a complex with cyclin C and phosphorylate the retinoblastoma protein (pRb) at serine 807/811, which is required for G0-G1 transition [10]. Furthermore, cdk3 seems to be expressed in various normal human tissues and cancer cell lines including glioblastoma and neuroblastoma cells [10–12]. Therefore, since CDK3 polymorphism is in a gene coding for a cell cycle protein and is in an intron region with no known diagnostic value and also the SNP had known allele frequencies in multiple populations, and the two alleles were both common, we have undertaken this project to find out the frequency of polymorphisms in India as preliminary study. The allele frequencies in our population are not available.