泌尿器科腫瘍学における分子研究の展望 : 発癌・転移機構(精巣腫瘍)

Abstract

自験例を対象として精巣腫瘍の発生, 進展, 抗癌剤耐性に関する分子生物学的検討を行った.その結果, 発生についてはKRAS2遺伝子やHLA-DR, HLA-DRB1の0405 alleleが関与している可能性が示唆された.進展にはWT1遺伝子産物の関与が示唆された.抗癌剤耐性に関してはp53遺伝子の下流にあるGMLの関与が推察された

Testicular germ cell tumor comprises about 1% of all the malignancies of males in Japan, and occurs in only one over 100, 000 males annually. A susceptibility gene may be located on the short arm of the chromosome 12. Among the genes in this region, the expression of the KRAS2 mRNA was increased in testicular cancer compared to the normal testicular tissue. By DNA typing, HLA-DR4 and 0405 allele in HLA-DRB1 showed high relative risk for testicular cancer. We analyzed the expression of the WT1 gene, reported to be a growth promoter for leukemia, by quantitative reverse transcription-PCR. Relative expression of the WT1 gene was significantly increased in high-stage cases than in low-stage cases, suggesting that WT1 could be useful as a tumor marker for progression of testicular cancers. Testicular germ cell tumors are usually very sensitive to chemotherapeutic agents such as cisplatin, and p53 has been reported to play an important role in chemosensitivity. Therefore, mutations of the p53 gene or other genes downstream may be responsible for their chemoresistance. The expression of the GML (GPI--anchored molecule like protein) gene was examined in testicular cancers. Its expression was not correlated with histology or stage. However, 4 refractory cases, 2 of which were recurrent cases from stage I and the others were at high stages, showed no expression of the GML mRNA. These interesting facts suggest that the expression of GML gene could be a good marker for the prognosis of testicular germ cell tumors.