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Mutation and expression of the p51 gene in human lung cancer.

ABSTRACT: A newly identified gene, p51, is a functional and structural homologue of the p53 gene and thus a Candidate tumor suppressor gene. To elucidate the role of the p51 gene in lung carcinogenesis, we determined the sequences of exon-intron boundaries and the 5'- and 3'-flanking regions of all the 15 coding exons and performed a mutation analysis, as well as detailed analysis for gene expression. A frameshift mutation was detected in 1 of 44 lung cancer cell lines, whereas no mutation was detected in 45 primary lung cancers. Thus, p51 mutation occurs only in a small subset of lung cancer. Expression of the p51 gene was detected in 23 of 43 cell lines by Northern blot analysis and 34 of 44 by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Thus, p51 expression is low or absent in a subset of lung cancer. The deltaN isotype of p51 transcripts was dominantly expressed in several cell lines, particularly in cell lines with high levels of p51 expression. Because the deltaN isotype encodes a protein that transdominantly suppresses the transactivation function of the TA type of p51, it is possible that p51 protein is not functionally active, even in lung cancer cells with p51 mRNA expression, due to expression of dominant-negative p51 protein. These results suggested that the p51 gene is inactive in a considerable proportion of lung cancers. RT-PCR analysis also revealed the presence of a novel type of mRNA transcript, p51delta, which lacks exons 12 and 13 by alternative splicing. The delta isotype was expressed in 18 of 44 lung cancer cell lines and in diverse normal tissues. Further analysis on p51 expression in cancerous as well as noncancerous cells will provide us with valuable information for the understanding of multiple functions of the p53 family proteins in human carcinogenesis.

SUBMITTER: Tani M

PROVIDER: S-EPMC1716054 | biostudies-literature | 1999 Apr

REPOSITORIES: biostudies-literature

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Mutation and expression of the p51 gene in human lung cancer.

Tani M M Shimizu K K Kawahara C C Kohno T T Ishimoto O O Ikawa S S Yokota J J

Neoplasia (New York, N.Y.) 19990401 1

A newly identified gene, p51, is a functional and structural homologue of the p53 gene and thus a Candidate tumor suppressor gene. To elucidate the role of the p51 gene in lung carcinogenesis, we determined the sequences of exon-intron boundaries and the 5'- and 3'-flanking regions of all the 15 coding exons and performed a mutation analysis, as well as detailed analysis for gene expression. A frameshift mutation was detected in 1 of 44 lung cancer cell lines, whereas no mutation was detected in ...[more]

PMID: 10935472

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Project description:BackgroundThe coexistence of double primaries of lung cancer (LC) and breast cancer (BC) are not uncommon in women, but there has been limited research conducted of their molecular association. To decipher the internal pathogenesis of LC in patients with concurrent BC and LC, this study explored the clinical factors and relationship between hormone receptor (HR) expression and epidermal growth factor receptor (EGFR) gene mutation.MethodsThe clinicopathological characteristics of 400 female patients clinically diagnosed with double primary LC and BC at Fudan University Shanghai Cancer Center were collected. Pathological discrimination was performed to further confirm the double primaries in patients with available tissues. LC samples were then examined to detect EGFR gene mutation status by PCR-based assays and HR expression by immunohistochemistry (IHC). As a control cohort, the characteristics of 114 consecutive patients with LC only were compared with the double-primary patient group.ResultsA total of 169 patients were pathologically confirmed with simultaneous LC and BC between January 2010 and October 2018. The dominant LC subtype was adenocarcinoma (ADC) (95.1%), and invasive ductal carcinoma (IDC) was the main BC subtype (71.0%). Synchronous and metachronous double primary BC-LC cases accounted for 39.1% and 60.9% of the patients, respectively. The absence of family cancer history was associated with a shorter interval between the two primary cancer diagnoses. Among 64 patients with EGFR mutations, 34.4% had HR-positive LC tissue, compared with 0/24 (0%) of those with EGFR wild-type LC (P<0.001). All of the patients with positive HR expression harbored an activating EGFR mutation (n=22); however, no correlation was observed in the control cohort.ConclusionsDouble primary BC-LC patients have distinctive clinicopathological features compared to those with LC only. The expression of HRs is significantly correlated with EGFR mutation status of LC tissues.

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Mutation and expression of the p51 gene in human lung cancer.

Publications

Mutation and expression of the p51 gene in human lung cancer.

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