Barrett’s esophagus cancer mechanisms – cell proliferation and cell cycle

By | March 23, 2012

Cell cycle is closely related with the tumor, the same in the Bar-rett adenocarcinoma of the esophagus to the evolution of the molecular mechanism also changes. Currently found in the process, the mechanisms involved in cell cycle regulation are the following:
Barrett's esophagus cancer mechanisms – cell proliferation and cell cycle proliferating cell nuclear antigen and Ki-67. PCNA is a cofactor for DNA synthesis, but also cell cycle from G1 to S phase of the conversion of a marker. Metaplasia in Barrett esophagus, PCNA expression in the height of dysplasia was significantly higher than low-grade dysplasia of the organization, and Ki-67 at a height of dysplasia and cancer tissues was significantly increased. Ki-67 reflects the proliferative (G1 phase, S phase, Gz phase and M phase) state of a cell nuclear antigen, and quiescent (G0 phase) cells without expression. Study found that dysplasia in Barrett esophagus to adenocarcinoma from the evolution, Ki-67 from the gland area and basal area to the expression of epithelial area is gradually increased. It is reasoned that with such a proliferation of cells in the tumor is formed when a clone.
Barrett's esophagus cancer mechanisms – cell proliferation and cell cycle p16. In human tumors, only p53 mutation is more common than p16 mutations. p16 is a tumor suppressor gene, located on chromosome 9p21. Under normal circumstances, p16 expression increased cell cycle arrest in G1 phase, the mechanism is able to inhibit the phosphorylation of Rb protein cyclin dependent kinase activity, the cell cycle can not enter S phase and DNA synthesis phase, this DNA can not be copied. Inactivation of p16 allows cell proliferation out of control, 9p21 heterozygous deletion was part of the inactivation of p16 alleles main reasons. The 9p21 loss of heterozygosity sites in the absence of dysplasia in Barrett esophagus metaplasia is rarely seen in film, but the relevance of esophageal adenocarcinoma in Barrett, this heterozygous deletion was 75% -91%. A study of esophageal cancer and precancerous lesions FHIT gene p16 promoter CPG island methylation was found in mild, moderate and severe dysplasia, squamous cell carcinoma in situ and invasive carcinoma were 95 cases of lesions p16 gene methylation frequencies were 22.73%, 59.09%, 78.57%, 64.86%; FHIT gene methylation frequencies were 22.73%, 45.45%, 64.29%, 67.57%. In the 10 cases of chronic esophagitis in 1 patient tissue p16 gene methylation, FHIT gene methylation was not found. In normal mucosa a mucosal dysplasia in a cancer tissue, p16 expression rate decreased. Thus, p16 and FHIT gene methylation exist in the precancerous lesion stage, possibly one of the events of early esophageal cancer.
Barrett's esophagus cancer mechanisms – cell proliferation and cell cycle growth factor and its receptor. TGF, EGF, EGFR, and FGF is involved in the process of esophageal carcinogenesis Barrett growth factor. TGF and EGF in the structure and function is similar, TGF binding to and induced activation of EGFR promoter gene in the nucleus. Barrett esophagus and esophageal adenocarcinoma, in the PCNA positive expression also have TGF District expression of intestinal metaplasia in the esophagus to dysplasia and adenocarcinoma of the development process, TGF, and FGF expression is gradually increased. These tips growth factor and its receptors are involved in the regulation of esophageal mucosal cell proliferation process. In addition, esophageal adenocarcinoma, if the expression of TGF and EGFR positive, then the prognosis is poor.
Barrett's esophagus cancer mechanisms – cell proliferation and cell cycle Rb gene. Rb gene is also involved in cell cycle regulation, which is located on chromosome 13q14. Cell growth stimulation signals can induce the production of cyclin-dependent kinases, and this kinase can Rb gene phosphorylation. Phosphorylation of Rb gene inactivation and to EGF after aggregation of cells from the quiescent into synthesis and mitosis. Rb gene mutation will make this the normal regulation of cell cycle disorder. In many tumors (including esophageal adenocarcinoma) can be seen in the Rb gene mutations and LOH. A recent study showed that in normal esophageal squamous epithelium and low grade dysplasia mucosa did not find Rb gene loss of heterozygosity, and in some high degree of dysplasia (1 / 12) and esophageal adenocarcinoma (5 / 27) in the there the loss of heterozygosity. Coppola immunohistochemistry found in Barrett metaplasia to dysplasia and mucosal adenocarcinoma in the process, Rb gene expression is decreased, so that, in some Barrett esophagus in the development of relevant, Rb gene is not involved in cell proliferation adjustment.

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