TAp63gamma can substitute for p53 in inducing expression of the maspin tumor suppressor.
Maspin is a Class II tumor suppressor protein and plays a role in tumor growth by inhibiting cellular invasion and motility. It is a member of the serpin family of protease inhibitors and has been shown to reduce angiogenesis. Maspin gene expression can be upregulated by the tumor suppressor p53. We tested 7 p53-related proteins of the p63 and p73 families for their ability to induce maspin expression. The p63 splice form TAp63gamma can substitute for p53 in activating the maspin promoter. TAp63gamma activates the promoter through the same consensus site as p53. In the DLD-1 colorectal adenocarcinoma cell line, harboring a tet-off regulated transgene, induction of TAp63gamma leads to an upregulation of maspin mRNA from the chromosomal gene. With a short lag phase also maspin protein levels are elevated after induced TAp63gamma expression. To assess a potential function of p63-dependent maspin upregulation in tumors we followed expression of p53, p63 and maspin by immunohistochemistry in hepatocellular carcinomas. Two types of tumors with wild-type or mutant p53 were assayed. Interestingly, the majority of tumors expressing only a mutated and inactive p53 protein nonetheless stain positive for maspin, whereas these tumors were positive for p63 protein expression. In summary, we show that TAp63gamma can substitute for p53 in transcriptional activation of the maspin tumor suppressor gene. TAp63gamma employs the same DNA recognition site for this activation as p53. We observe expression patterns of p53, p63 and maspin proteins in tumor tissue that may indicate also a function of maspin induction by p63 in tumors.
Spiesbach
Katja
K
Department of Internal Medicine II, University of Leipzig, Leipzig, Germany.
Tannapfel
Andrea
A
Mössner
Joachim
J
Engeland
Kurt
K
D017398:Alternative Splicing; D001665:Binding Sites; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000473:pathology; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000096:biosynthesis* / Q000378:metabolism; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D025521:Tumor Suppressor Proteins; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D012313:RNA; D008156:Luciferases