Quantitative analysis of aromatase, sulfatase and 17beta-HSD(1) mRNA expression in soft tissue metastases of breast cancer.
Expression of the estrogen-synthesizing genes aromatase, steroid sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type1 (17beta-HSD(1)) has been shown to be up-regulated in primary breast cancer tissue but their expression status in metastatic tumor tissue has yet to be determined. The mRNA expression levels of the three estrogen-synthesizing genes as well as of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and cyclooxygenase (COX)-2, all of which have been reported to up-regulate the estrogen-synthesizing genes, were determined by means of a real-time PCR assay in 100 primary breast cancer tissues and 15 soft tissue metastases. In addition, PCR-gel electrophoresis was used to determine the proportion (%) of promoter (l.4, l.3, Pll and l.7) usage of aromatase. Aromatase and STS mRNA levels were significantly (P=0.04 and P=0.03, respectively) higher in soft tissue metastases than in primary tumors, while 17beta-HSD(1) mRNA levels tended (P=0.09) to be higher. The proportions of the promoter usages were very similar for primary tumors and soft tissue metastases, and the mRNA levels of TNF-alpha, IL-6 and COX-2 were not significantly different. Levels of aromatase, STS and 17beta-HSD(1) mRNA are up-regulated in soft tissue metastases compared to those in primary tumors, suggesting that intra-tumoral estrogen synthesis may play a significant role in the growth stimulation of tumor cells in soft tissue metastases as in primary tumors. TNF-alpha, IL-6 and COX-2, on the other hand, are unlikely to be implicated in this up-regulation.
Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita-shi, Osaka 565-0871, Japan.
Natsumi
N
Irahara
Yasuo
Y
Miyoshi
Tetsuya
T
Taguchi
Yasuhiro
Y
Tamaki
Shinzaburo
S
Noguchi
D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics*; D000328:Adult; D000368:Aged; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012983:Soft Tissue Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D043266:Steryl-Sulfatase / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015850:Interleukin-6; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D043266:Steryl-Sulfatase