Effect of sodium butyrate on the expression of retinoblastoma (RB1) and P53 gene and phosphorylation of retinoblastoma protein in human colon tumor cell line HT29.
Sodium butyrate is known to induce morphological and biochemical changes associated with cell differentiation in some colon tumor cell lines including HT29. In our present study we observed that sodium butyrate treatment caused a decrease in the level of expression of RB1 gene on day seven of butyrate treatment but a gradual six to sevenfold decrease in the level of expression of p53 gene. Western blot analysis revealed a decrease in the level of the phosphorylated form of Rb protein (pRb) and an increase in the level of underphosphorylated pRb as compared to the control cells. These changes in the phosphorylation level were observed from day three of sodium butyrate treatment. In addition, the flat foci forming large differentiated cells also began to appear after 3 days of sodium butyrate treatment. In this study, we are able to show that, besides induction of differentiation, sodium butyrate treatment can also cause a reversal in the phosphorylation status of the pRb in colon tumor cell line HT29. These results suggest that the phosphorylation level of pRb could be associated with the cell differentiation process in human colonic epithelium and as a consequence in its neoplastic development.
Gope
R
R
Creighton University School of Medicine, Creighton Cancer Center, Omaha, NE 68178.
Gope
M L
ML
D000230:Adenocarcinoma / Q000473:pathology*; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002454:Cell Differentiation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D003864:Depression, Chemical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016161:Genes, Retinoblastoma / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D002087:Butyrates; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D020148:Butyric Acid