Unknown,Transcriptomics,Genomics,Proteomics

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Frequent Loss-of-Function Mutations in MLK4 Suppresses Signaling in the JNK-cJUN-p21/p15 Pathway to Promote Growth of Colon Cancer Cells

ABSTRACT: The goal of the study was to evaluate the influence of mutations in MLK4 on the protein function and the process of tumorigenesis in colorectal cancers. Biochemical data imply that a majority of MLK4 mutations in colon cancer are loss-of-function, including, E314K and Y330H mutations. Two colorectal cell lines, HCT15 and HT115, harboring MLK4 loss-of-function mutations, Y330H and E314K respectively, were used in the study. To evaluate the consequences of loss-of-function MLK4 mutations in those colon cancer cell lines, HCT15 and HT115 cell lines were generated where expression of MLK4-WT (in HCT15 and HT115 cell lines) or MLK4-Y330H (in HCT15 cells) or MLK4-E314K (in HT115 cells) can be induced by tetracycline. The reconstitution of MLK4-WT in colon cancer cells reduced viability, proliferation and ability to form colonies as well as significantly slowed down the tumor growth in mouse xenografts. To investigate the downstream effectors of MLK4 that mediate the above effects, we transcriptionally profiled colon cancer cell lines after MLK4-WT reconstitution. The data indicates that re-expression of functional MLK4 leads to reduction in cell proliferation, likely due to increased expression of cJUN and cdk inhibitors (p15 or p21). HCT15 and HT115 were treated with tetracycline for 24 hours to induce expression of MLK4. Cells were harvested and mRNA was isolated using Qiagen RNeasy Plus Mini Kit. Samples were hybridized to Affymetrix Human U133 Plus 2.0 array. Experiments were performed in triplicates for every sample. Induction of Y330H in HCT15 cells and MLK4-E314K in HT115 cells was used as a control.

ORGANISM(S): Homo sapiens

SUBMITTER: Anna Marusiak

PROVIDER: E-GEOD-59196 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Frequent Loss-of-Function Mutations in MLK4 Suppresses Signaling in the JNK-cJUN-p21/p15 Pathway to Promote Growth of Colon Cancer Cells

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