A Study On The Expression Of P63 Gene In Human Non-small Cell Lung Cancer Tissues

p63 is another member of the p53 family. The p63 gene, mapping to 3q27-29, contains 15 exons and encodes at least six different proteins due to alternative promoter usage and alternative splicing, they all share a common open reading frame. The mRNA transcribed from the most 5' promoter encode p63 isoforms containing a transcription activation domain(TAp63), while transcription from the 3' promoter results in p63 isoforms that lack the TA domain and are referred to as ΔNp63. The alternative splicing results in synthesis of TA and ΔN isoforms with three different C-termini, α,β andγ. Like p73, p63 is rarely mutated in human cancers, making a tumour suppressor function unlikely. The TA and ΔN isoforms of p63 have opposing functions on inducing cell cycle arrest and apoptosis. The overexpression of ΔNp63 in tumours can suppress the apoptosis and accelerate the prolifetation of tumour, so ΔNp63 is an oncogene amplified in human tumours. Reverse transcriptase polymerase chain reaction(RT-PCR) and imunohistochemical staining technique was used to investigate the significance of the expression of TA and ΔN isoforms of p63 gene in 40 non-small cell lung carcinoma(NSCLC) tissues, para-cancer tissues and 10 benign lung lesion tissues. To understand the manner of p63 gene expression in NSCLC and to explore the relationship between p63 gene transcript expression and oncogenesis, development and clinical characteristic of NSCLC. Based on the study we can obtained the following results: 1. The expression of p63 gene can be found in 19/40 NSCLC tissues, including 18 squamous cell carcinomas(18/23) and one broncho-alveolar carcinoma(1/6). There is no clearly expression of p63 gene in para-cancer and benign lesion tissues. The expression level of p63 mRNA in the cancer tissues was significantly higher than that in para-cancer and benign lesion tissues(P<0.01). There is significantly difference of the p63 expression level between squamous cell carcinoma and other histoclassifications of NSCLC(P<0.01). No significantly difference of the p63 mRNA and protein expression level can be found between para-cancer and benign lesion tissues(P>0.05). 2. ΔNp63 is overexpressed in NSCLC(especially in squamous cell carcinoma), and the expression of TAp63 was not observed in all of cancer, para-cancer and benign lesion tissues. 3. The p63 mRNA and protein expression level is only related to the histoclassifications of NSCLC. No significantly difference was observed between p63 expression and sex, age, smoking history and P-TNM stages of the cancer(P>0.05).Conclusions: 1. The overexpression of p63 gene can be observed in squamous cell carcinoma rather than other histoclassifications of NSCLC. This suggests that p63 maybe plays a role in the oncogenesis and development of squamous cell carcinoma. 2. The amplification was limited to ΔN isoforms of p63, which support the idea that ΔNp63 is an oncogene rather than a tomour suppressor gene and plays a important role in the oncogenesis and development of NSCLC especially in squamous cell carcinoma.