Mutational analysis of p51A/TAp63gamma, a p53 homolog, in non-small cell lung cancer and breast cancer

p51, a novel family member of human p53, is a recently identified candidate tumor suppressor gene mapped at chromosome 3q28. Like p53, p51 was found to activate p21Waf1/Cip1 and to induce apoptosis. Since the DNA loss at 3q is reported in several cancers including non-small cell lung cancer (NSCLC),...

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Published inOncogene Vol. 18; no. 25; p. 3761
Main Authors Sunahara, M, Shishikura, T, Takahashi, M, Todo, S, Yamamoto, N, Kimura, H, Kato, S, Ishioka, C, Ikawa, S, Ikawa, Y, Nakagawara, A
Format Journal Article
LanguageEnglish
Published England 24.06.1999
Subjects
Adult
Aged
Aged, 80 and over
Base Sequence
Breast Neoplasms - genetics
Carcinoma, Non-Small-Cell Lung - genetics
DNA Mutational Analysis
DNA, Complementary - genetics
DNA, Neoplasm - genetics
DNA-Binding Proteins - genetics
Female
Genes, Tumor Suppressor
Humans
Lung Neoplasms - genetics
Male
Middle Aged
Molecular Sequence Data
Neoplasm Proteins - genetics
Phosphoproteins
Polymorphism, Single-Stranded Conformational
Protein Isoforms - genetics
Reverse Transcriptase Polymerase Chain Reaction
Saccharomyces cerevisiae - genetics
Trans-Activators
Transcription Factors
Tumor Suppressor Proteins
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Summary:p51, a novel family member of human p53, is a recently identified candidate tumor suppressor gene mapped at chromosome 3q28. Like p53, p51 was found to activate p21Waf1/Cip1 and to induce apoptosis. Since the DNA loss at 3q is reported in several cancers including non-small cell lung cancer (NSCLC), we screened for mutations in p51A (TAp63gamma), an isoform of p51 with short C-terminal region, in 80 NSCLCs as well as 85 breast cancers by RT-PCR single strand conformation polymorphism (SSCP) analysis and DNA sequencing. In NSCLCs, p51 was expressed in most tumors at variable levels and we found three missense and one silent mutations: Gln31His (transactivation domain) in two tumors, Ala148Pro (DNA-binding domain) and Leu248Leu (DNA-binding domain). In the tumor with Ala148Pro or the silent mutation, only the mutant gene appeared to be expressed. The modified FASAY method to test the ability of yeast expressing p51A cDNA to grow in medium lacking histidine has revealed that Ala148Pro results in a loss of function, while Gln31His does not. In contrast to NSCLC, no mutation was observed in all 85 breast cancers by the similar method. Our results suggest that, because of infrequent mutation, p51 may not be a Knudson type tumor suppressor in most NSCLCs and breast cancers. Nevertheless, in at least a part of NSCLC, p51 may play a certain role in carcinogenesis in a tissue-specific manner.
ISSN:0950-9232