Expression of mRNAs for succinate dehydrogenase subunits and related genes in pheochromocytoma.
Mutations in the genes encoding succinate dehydrogenase (SDH) have been associated with susceptibility to pheochromocytoma. However, few reports have examined the level of SDH mRNAs expression. In this study, we examined the level of expression of mRNAs encoding SDHB, SDHC, and SDHD in pheochromocytoma, pheochromocytoma subgroups, and normal adrenal gland, and compared the expression of these genes to the level of expression of related genes in the same tissues. The mean relative level of expression of SDHB, SDHC, SDHD and VHL mRNA was 28.7+/-6.2%, 16.6+/-4.8%, 214+/-47.5% and 25.9+/-8.2%, respectively, in pheochromocytoma tissues compared to normal adrenal gland. Furthermore, the mean relative level of the RET proto-oncogene mRNA was 707+/-149% in pheochromocytoma compared to normal adrenal gland. The level of expression of the SDH genes was highly correlated in each individual sample (P<0.0001). The level of expression of the SDH mRNAs correlated with the level of VHL mRNA (P<0.0001), but not with the level of RET mRNA. The level of SDH mRNAs expression also correlated with the expression of phenylethanolamine N-methyl transferase (PNMT), an adrenaline synthesizing enzyme (P<0.01), which may explain the correlation between SDH expression and adrenaline content (P<0.05). The level of SDH mRNAs expression correlated strongly with the expression of VEGF mRNA (P<0.0001). In multiple endocrine neoplasia (MEN) 2a, the expression of the SDH genes and VHL mRNA was significantly higher than that observed in adrenal or extra-adrenal pheochromocytoma. The expression of the corticotropin-releasing hormone (CRH) mRNA was significantly higher in extra-adrenal pheochromocytoma than in adrenal pheochromocytoma or MEN2a. Thus, tumor-specific gene expression exists in pheochromocytoma, which may explain the characteristics of the tumor.
Isobe
Kazumasa
K
Department of Clinical Pathology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennnoudai, Tsukuba, Ibaraki 305-8575, Japan. k-isobe@md.tsukuba.ac.jp
Nissato
Sumiko
S
Tatsuno
Ichiro
I
Yashiro
Toru
T
Takekoshi
Kazuhiro
K
Kawakami
Yasushi
Y
D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010673:Pheochromocytoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics*; D013385:Succinate Dehydrogenase / Q000235:genetics*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D013385:Succinate Dehydrogenase