| Barrett esophagus(BE)is a metaplastic process in which the normalquamous epithelium of the distal esophagus is replaced by columnar linedepithelium and is the result of chronic gastroesophageal reflux,may beassociated with intestinal metaplasia or no intestinal metaplasia, accompaniedby special intestinal epithelial metaplasia is a precancerous lesion ofesophageal adenocarcinoma(EC). The patients with Barrett's esophagus toesophageal adenocarcinoma probability is30-50times the general population,80%of esophageal adenocarcinoma develop from the BE. Clinical studies andepidemiological surveys show that the increased incidence of esophagealadenocarcinoma one of the fastest growing tumor, and rising up to350%inWestern countries, its growth rate tends to the top of the malignant tumors inthe1970s. In China, with the Westernization diet, Barrett esophagus andesophageal adenocarcinoma incidence increased year by year. But thepathogenesis of BE is still unclear, more and more scholars believe that BEcells derived from stem cells that it can explain the BE cell differentiation,Xia Wang et al show that residual embryonic cell as precuesors of a Barrett's–like meaplasia in addition to other domestic and foreign studies haveconfirmed that key genes in the PI3K/Akt/mTOR signal pathway isupregulated in Barrett's esophagus induced by bile, suggesting that thesignaling pathways involved in the pathogenesis of Barrett's esophagus in themodel of Barrett's esophagus in the rat reflux.Objective: In this study,We determine expression levels of PI3K,Akt,CyclinD1and p-mTOR, which are considered to be key genes ofPI3K/Akt/mTOR signal pathway, in the different-month-old fetus esophagus,in order to explore the PI3K/Akt/mTOR signal pathway during development ofhuman esophagus,to investigate the pathogenesis of Barrett's esophagus and to verify that is a congenital disease.Methods: Collect different months of normal esophagus(NE) of fetal(April, May, June, July6cases each),HE staining then pathologicalexamination of the organizational structure under the light microscope, detectexpression of PI3K, Akt, CyclinD1and p-mTOR in different months fetalesophagus with both immunohistochemistry and Western-Blotting.Results:1Immunohistochemical staining1.1PI3K protein is observed in the nucleus mainly, some cytoplasm canalso be found: in the April month-old fetal esophageal strong positive,5-7month-old fetus the esophagus is weak positive to positive expression. PI3Kprotein expression is gradually declined with the increase of the conceptus age.The MOD differences among the groups are statistically significant (P <0.05).1.2Akt protein expression found in nucleus, some can also be found inthe cytoplasm: in the April month-old fetal esophageal strong expression,5-7month-old fetus the esophagus is weak positive to positive expression. PI3Kprotein expression is gradually declined with the increase of the conceptus age.The MOD differences among the groups are statistically significant (P <0.05).1.3p-mTOR protein expression found in nucleus, some can also be foundin the cytoplasm: in the April month-old fetal esophageal strong expression,5-7month-old fetus the esophagus is weak positive to positive expression.P-MOR protein expression is gradually declined with the increase of theconceptus age. The MOD differences among the groups are statisticallysignificant (P <0.05).1.4CyclinD1protein expression found in the cytoplasm, some can alsobe found in nucleus: in the April month-old fetal esophageal is positive,5-7month-old fetus the esophagus is negative to weak positive expression.CyclinD1protein expression is gradually declined with the increase of theconceptus age. The MOD differences among the groups are statisticallysignificant (P <0.05).1.5The gene expression analysis: there is a good correlation between Akt and PI3K (r=0.849, P＜0.05), Akt and CyclinD1(r=0.846, P＜0.05),Akt andp-mTOR (r=0.699, P＜0.05), PI3K and CyclinD1(r=0.903, P＜0.05), PI3Kand p-mTOR (r=0.888, P＜0.05),CyclinD1and p-mTOR (r=0.852, P＜0.05).2Western blot2.1PI3K protein expression decreased gradually with the increase of thefetal conceptus age: the optical density ratio in April and May, June, July wasstatistically significant (P＜0.05),But the optical density ratio between May,June and July are no statistically significant (P＞0.05)2.2Akt protein expression decreased gradually with the increase of thefetal conceptus age: the differences of the optical density ratio between thegroups are statistically significant (P＜0.05).2.3CyclinD1protein expression decreased gradually with the increase ofthe fetal conceptus age: the optical density ratio in April and May, June, Julyare statistically significant (P＜0.05),But the optical density ratio among May,June and July are no statistically significant(P＞0.05)2.4p-mTOR protein expression decreased gradually with the increase ofthe fetal conceptus age: the optical density ratio between April and July isstatistically significant (P＜0.05),But the differences of optical density ratioamong April, May and June are no statistically significant(P＞0.05) thedifferences of optical density ratio among May June and July are nostatistically significant(p＞0.05)2.5The gene expression analysis: there is a good correlation between Aktand PI3K(r=0.44, P＜0.05),Akt and CyclinD1(r=0.846, P＜0.05) Akt andp-mTOR(r=0.406, P＜0.05),PI3K and CyclinD1(r=0.251, P＜0.05) PI3K andp-mTOR(r=0.351, P＜0.05),CyclinD1and p-mTOR (r=0.852, P＜0.05).Thecorrelation between the following protein is not so good: Akt and CyclinD1(r=0.306, P＞0.05), Cyclin D1and p-mTOR (r=0.221, P＞0.05)Conclusions:In fetal esophagus,the expression of each key gene in PI3K/Akt/mTORsignal pathways declines with the increase of months, suggesting that there isa link between the signal pathways and differentiation and apoptosis in the process of development of the fetal esophagus. PI3K/Akt/mTOR signalpathway involved in the pathogenesis of Barrett's esophagus, suggesting thatthe Barrett's esophagus may be thus differentiated from stem cells areactivated,be determined by congenital causes. |
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