Introduction of tumor suppressor genes

By | March 31, 2012

In recent years, with the number of new tumor suppressor gene cloning and identification of continuous, tumor suppressor genes has become a hot spot in the life science research.
Introduction of tumor suppressor genes (a) p53 gene
p53 gene is the most extensive genetic studies of tumor suppressor genes. full-length p53 gene 20kb, located on human chromosome 17p13.1, consists of 11 exons. Protein-DNA and protein with a protein binding function. Now clear that p53 is a negative regulator of cell cycle factors, and cell cycle regulation, DNA repair, cell differentiation and apoptosis and other biological functions. p53 gene has two wild-type and mutant, and its products also have wild-type and mutant. Wild-type P53 protein half-life is very short, only 15-30 minutes. Thus, in normal cells could not be detected in the P53 protein. Transcriptional regulation of P53 protein can be synthesized in the DNA began to repair the damage before the induction of DNA damage does not repair or apoptosis. DNA damage is activation of wild-type P53 protein in the major molecular events. Thus, the lack of p53 function in wild-type cells can not repair damage DNA, eventually evolved into the tumor cells. Tumor cells, p53 gene inactivation are two forms: one is the p53 gene mutation, the coding loss of tumor suppression function of the product; the other is the p53 gene and its encoded product are still capable of maintaining its normal wild-type structure, but with other types of virus or cell proteins combine to form a stable protein complex, the change in the wild-type P53 protein conformation, so that the function of P53 protein inactivation and leads to cell appeared; malignant transformation. The main methods of p53 gene mutation showed point mutation, deletion mutation, insertion mutation, frameshift mutations and gene rearrangements.
Introduction of tumor suppressor genes (b) Rb gene
Retinoblastoma gene (retinoblastoma gene) referred to as the Rb gene, Rb gene is located on human chromosome 13q14, total length of about 200kb, with 27 exons and 26 introns, transcripts of approximately 4.7kb of the mRNA, encoding the 928 amino acid composition, molecular weight of 105-110kDa nuclear phosphoprotein RboRb protein within the state when the impact of Rb gene in regulating cell growth and differentiation of the main form. Later, people many different types of tumor cells have Rb protein Rb gene mutations or loss of function. With the Rb gene and protein structure and function of the continuous in-depth study found that, like protein and P53 proteins, on cell growth, differentiation, cell cycle, cell biology has an important role in the regulation of behavior.
Hb gene abnormalities mainly for allelic loss and gene mutations. Exception of Rb protein in SCLC in 90% or more, in NSCLC was 15% UI called Rb gene mutations in lung cancer means there is allelic loss, nonsense mutations or abnormal. Trying to find lung cancer in the individual research Rb gene point mutations, but found that most mutations are caused by the allelic loss of the truncated Rb gene. Has also been reported in Rb gene "pocket" (pocket) change the regional rare HI Concurrent protection can lead to phosphorylation of Rb, as well as genes encoding proteins binding to cancer formation. With further study of Rb gene was found on the structure and function of the total very close relationship with the pll0Rb related genes. Study found that these genes are also unusual in the production. Found in a SCLC cell line cut p130 gene (locus of a point mutation, this change result in the deletion of exon 2 and the truncated form of protein.
Introduction of tumor suppressor genes (c) p16 gene
p16 gene is located on 9p21, full-length 8.5kb, by two introns and three exons. Three common coding exons, a known cyclin-dependent inhibition of stimulated Li a protein of 148 residues bitterness. Since the gene with a variety of tumors, so called multiple tumor system genes. Because the molecular weight is based MTSI 15.8kDa, which is also known as p16 gene, officially named after the human cyclin-dependent kinase inhibitor 2 key factors. p16 and cyclin D (cyclin D) combination of competition and CDK4, even combined p16 and CDK4 could specifically inhibit the activity of CDK4. When the p16 gene usually but not when the normal expression of cyclin D and CDK4 preferred combination of a long lost control of the cell, which appears phenotype.
Distribution of p16 gene abnormality of tumor spectrum is very broad, including almost the majority of human tumors, such as brain tumors, head and neck cancer, lung cancer, esophageal cancer, adenocarcinoma film, hazy bladder cancer, breast cancer, renal cancer, lymphoma and from leukemia and so on. Abnormal p16 gene on biological behavior and prognosis of lung cancer relationship, most of the research results suggest, p16 gene abnormalities and NSCLI evolution and metastasis. Immunohistochemistry, P16 protein expression level of NSCLC loss was positively correlated with the clinical stage. But there are also results do not support this view; that the absence of P16 protein expression and NSCLC, clinical stage and prognosis of independence.
Introduction of tumor suppressor genes (d) PTEN gene
PTEN gene located on chromosome 10q23.3 Region, 9 exons, encoding 40 amino acids of the protein in writing, the product of the relative molecular weight 56kDao Currently, researchers found that PTEN has the following features; in the normal development of embryos; through induced G1 arrest or apoptosis, inhibit cell growth; inhibition of telomerase; inhibited cell migration, spreading, and local education laws.
Findings, PTEN gene abnormalities may be present in glioblastoma, prostate cancer, renal cell carcinoma, breast and lung cancer and other tumors. Mainly through allelic loss, gene mutation and methylation way that the gene inactivation. PTEN gene mutation, including deletion mutations present type, missense mutation, nonsense mutations and mRNA element shear disorders. PTEN mutations are most common in exons 3,5 and 8, and often occur in chromosome! 10q loss of heterozygosity of tumor, multiple mutations in one allele, and frameshift change, and other common nonsense mutation. PTEN gene mutation is present in a small number of lung cancer and small cell lung cancer than non-small cell lung cancer PTEN gene mutation rate, number of lung cancer cell lines! Were found to have homozygous PTEN gene deletion.
It is noteworthy that, in the l chromosome 9 have a PTEN pseudogene, and 98% of coding sequence homology. Therefore, analysis of PTEN gene mutation, will pseudogene interference.

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