Assessment Of Changes In Isoforms Of MDM2 Gene, Before And After The Effect Of 5-Fluorouracil In Esophageal Cancer CellLines MKYSE-30)

Gastrointestinal cancers MGC) are prevalent cancers in the worldwide. Esophageal squamous cellcarcinoma MESCC) is the most human common cancer in the gastrointestinal tract. Genetic factorsand oncogenes have a critical role in the development of the disease. A mouse double minute 2homolog MMDM2) is a significant negative regulator of the p53 tumor suppressor. Mdm2 inoverexpressed in the most human malignant tumors. It is noteworthy that, more than 40 differentsplice variants of MDM2 transcripts have been identified both tumor and normal tissues. The mostimportant three of MDM2 splice variants are Mdm2-A, Mdm2-B, and Mdm2-C. In cancer cells, theMdm2 protein often contributes to change molecular programs that increase growth-promotingsignals and decrease cell death signals. The p53 is introduced as an important growth inhibitoryprogram into noncancerous cells. The anti-cancer peptide PNC-27, containing the MDM2-bindingdomain of p53, may target MDM2. Our aim of this study was to assess the effects of MDM2 variantson chemotherapy samples. In this study, cell lines KYSE-30, before and after chemotherapy by 5-fluorouracil, was examined for MDM2 mRNA splicing variants by Nested RT-PCR and sequencingtechniques. mRNA MDM2 was detected in cell lines KYSE-30. Alternatively MDM2 type 1 splicedvariants was indicated in KYSE-30 after chemotherapy by 5-fluorouracil. Moreover, two splicedforms of MDM2 were detected in KYSE-30. Our results indicate that with the use of 5-fluorouracil,can create some new isoforms and disappear some isoform. Overall, our results suggest thatchemotherapy with alteration in MDM2 isoforms expression can be assisted in targeted therapy byPNC27.