SAYA Hideyuki Kumamoto University School of Medicine, Department of Tumor Genetics and Biology, Professor, 医学部, 教授 (80264282)
ANDO Masayuki Kumamoto University School of Medicine, First Department of Internal Medicine, Professor, 医学部, 教授 (00040204)
|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 2000 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1999 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
We examined expressions of tumor suppressor gene(p53), adhesion molecules(CD44 isoforms) and carcinogenic products(nitric oxide synthase : NOS) to investigate about correlation between pulomonary firosis and carcinogenesis.
(1) Status of tumor suppressor gene p53 expression in lung cancer tissue, fibrotic tissue and non-tumorous tissue : We used an system of yeast p53 functional assay to examine an function of p53. We difined that p53 mutation occurred 63% of examined samples drived from primary lung cancer tissue(Int J Oncol., 12 ; 525-533, 1998). On the other hand, we could not comfirm that p53 mutation significantly occurred examined samples drived from pulmonary fibrosis tissue and also non-tumorous lung tissue.
(2) Expression of adhesion molecules CD44 isoforms in lung cancer tissue, fibrotic tissue and non-tumorous tissue : We suggested that we could diagnosed whether sample specimens were malignancy or not from changes of CD44 isoforms ratio(J Natl Cancer Inst., 90 ; 307-315, 199
8). Furthermore, CD44 cleavage plays a critical role in an efficient cell-detachment from a hyaluronate substrate during the cell migration and consequently promotes CD44-mediated cancer cell migration.(Oncogene.18 ; 1435-46, 1999) and also the Rho family proteins play a role in regulation of CD44 distribution and cleavage(J B C., 274 ; 25525-34, 1999). We could not find out any differences in fibrous lesions and also non-tumorous lesion about expressions of CD44 isoforms pattern.
(3) Correlation between expressions of nitric oxide synthase(NOS) and p53 mutations in lung tissues : NO(nitric oxide) induces mutation in the p53 tumor suppressor gene ; we therefore analyzed the relationship between NO synthase(NOS) activity and p53 gene status in early-stage lung adenocarcinoma. NO has potential mutagenic and carcinogenic activity, and may play important roles in human lung adenocarcinoma(Jpn J Cancer Res., 89 ; 696-702, 1998). However, levels of NOS expression were unstable and we couldn't confirm high expression of bNOS in fibrotic lesions. We suggested that expressions of p53 mutation, CD44 isoforms and NOS were heterogeneous different from cancerous lesions.
間質性肺炎部分を含めた非癌病変部ではCD44 splicing patternに差はなく、CD44Hのみが発現し、抗CD44H抗体を用いた場合には癌組織のみならず正常間質も染色された。また、抗CD44R1抗体を用いた免疫組織染色では癌細胞表面が特異的に染色されたが、癌部に隣接した部分の気管支上皮や肺胞マクロファージも染色された。
(3)肺癌組織におけるnitric oxide synthase (NOS)発現とp53遺伝子変異の相関
肺腺癌は他の組織型に較べ有意にNOSが高く、isoformの中でbNOSの高発現を明らかにした。1期肺腺癌を対象としてp53変異とNOS発現は相関し、NOS産生高値群は有意にp53変異の頻度が高く、肺腺癌ではNOS発現が生物学的悪性化に関与することが示唆されたが、間質性肺炎部分においてはNOS発現は一定せずisoform bNOSが高発現か否かは不明である。 Less