Early overexpression of Cdk4 and possible role of KRF and c-myc in chewing tobacco mediated oral cancer development

• Published in: Molecular biology reports 2003-12, Vol.30 (4), p.207-213
• Main Authors: Mishra, Rajakishore, Das, Bibhu Ranjan
• Format: Article
• Language: English
• Subjects: Base Sequence; Binding Sites; c-myc gene; Cancer; CdK4 gene; chewing tobacco; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinases - genetics; Cyclin-Dependent Kinases - metabolism; DNA Footprinting; Female; Gene Expression Regulation, Neoplastic; Humans; Kinases; Male; Middle Aged; Mouth Mucosa - cytology; Mouth Mucosa - metabolism; Mouth Mucosa - pathology; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Neoplasm Staging; Oral cancer; Promoter Regions, Genetic; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Tobacco, Smokeless - adverse effects; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1023/A:1026384402585

Cyclin Dependent Kinase 4 (Cdk4) is known to be an oncogene and is involved in various cancers. It is over-expressed either by genomic amplification or by c-myc dependent manner. Our preliminary results indicate high expression of protein and mRNA as well as absence of genomic amplification in early oral cancer development. One transcription factor (TF) binding site has been detected from -281 to -298 by using DNase I foot printing and confirmed by electrophoretic mobility shift assay. This is a novel DNA sequence. The recruitment of this new TF as well as the earlier reported c-myc was analyzed in various stage of oral cancer development. The binding activity of the new TF is present in normal tissues and observed more in initial stage samples whereas c-myc expression was absent in normal and more in higher stage of oral cancer development. On the basis of these findings we propose the new TF to be a possible CdK4 Regulating Factor (KRF). This might maintain the basal level transcription in normal and activates Cdk4 transcription in the initial stage, where as the same role is carried by c-myc in higher stage of chewing tobacco mediated oral cancer development.