Lung Tissue Of P16 Mrna And Protein Expression And Gene Abnormal Methylation Of The Study

Background: With development of the molecular biology, some oncogene and tumor suppressor gene have been proved to be the associated gene of lung cancer, such as Rb, p53, p16, nm23, APH, MCC, APC. Inactivation of tumor suppressor gene is a very important event in the carcinogenesis and development of lung cancer. The reason of tumor suppression gene inactivation is an allelic loss and the remain allele has mutation or promoter hypermethylation. The allelic loss is caused by the chromosome deletion, and often accompany with the loss of heterozygosity (LOH). 9p21 LOH is existed in. The p16 tumor suppressor gene that maps to chromosome band 9p21, which proved by Kamb in 1994 for the first time. Once the p16 gene is abnomal, the growth of cells will be uncon-troled.The p16 protein is one of the cyclins dependent kinases inhibitors (CKIs). Cyclins-cyclins dependent kinases(CDK)-cyclins dependent kinases inhibitors CKIs) system plays an important role in the cell cycle. The p16 protein inhibit the CDK4 activity through combine with CDK4 to prevent the cell from G1 to S and inhibit cells growth. Otherwise, CDK4 is activated by combined with cyclins and make Rb protein phosphomated. Phosphomated Rb will release some translated factors and promote the cell growth without control. CDKs. Cyclin and CDKIs are very important to understant the molecular mechanism of lung cancer.p16 gene is located on chromsome 9p21. The total length of cDNA is 8. 5 kb, consists of three exons and two introns. The exon 1 is 126bp,the exon 2 is 307bp and the exon 3 is 11bp. p16 gene encodes the protein of 16KD, consists of 156 amino acid. Kamb and their group studied the p16 gene in various of cell lines derived from all histologic types of human tumors. Their results are the deletion of p16 gene is existed in 50% tumor cell lines. In which the highest 71% , the second is60% 58% 56% 33% 25% ovarian cancer29%. They also find the p16 mRNA is negative in all p16 DNA deleted tumor cell lines by RT -PCR method. So the author considered that the homozygous deletion of the p16gene make the transcription silence and results in p16 gene inactivation. Volen-then reported the pl6 mRNA deletion is found in 16 cases of all 28 cases. They also suggested that the deletion of gene is the main mechanism of p16 gene dysfunction. Cao detected the p16 gene mRNA expression in non - small cell lung cancer (NSCLC) and found that the deletion of mRNA is 22. 6% (7/31) but it has no relation to the small cell lung cancer ( SCLC). They considerd that the change of p16 gene may play an important role in the tumorigenesis of non -small cell lung cancer. Washimi supposed that the p16 gene is an important molecular event in the lung cancer, especially in the NSCLC. The translated protein product is absence for the mRNA deletion and cause the cell malignant transformation. It has been confirmed in lung cancer, esophageal carcinoma, colon cacinoma, breast carcinoma . Jin studied the expression of the p16 protein in 106 early NSCLC cases by immunohistochemistry. In their research, the p16 protein is expressed in 54% cases and the positive cases has a longer post - operation living-time than protein negative cases. Hung.also found that 36.6% NSCLC are p16 protein negative and the abnormal expression is closely related to the squamous cell cancers. It is rare in adenocarcinomas and has no effect on prognosis. The negative protein cases of squamous cell cancers has poor prognosis.It is also observed in the research of lung cancer that GC island in the p16 gene exon 1 were methylated in all cases. Hypermethylated of pi6 gene 5'-CpG island make the gene transcription silence. So 5'-CpG island methylation is the main mechanism of the p16 gene inactivation. Okamoto considered that the p16 gene methylation may be important in NSCLC because no p16 gene deletion was found in 25 primary NSCLC. So they supposed that the 5CpG island of p16 gene are methlated and blocked the p16 gene transcription. Belinsky confirmed that the methylation of the p16 gene may be an early event o...