These results suggest that the clinical response to docetaxel can be predicted by gene expression patterns in biopsy samples. The results also suggest that one of the molecular mechanisms of the resistance is activation of a group of redox genes.

Estradiol (E2) and estrone (E1) levels as well as mRNA expression levels of aromatase, sulfatase and 17␤-hydroxysteroid dehydrogenase type 1 (17␤-HSD1) in breast cancer tissues were studied to elucidate the mechanism involved in the maintenance of the intratumoral high E2 levels in postmenopausal patients with very low serum E2 levels. Intratumoral E2 levels of postmenopausal patients (127.2 ؎ 17.5 pg/g) (mean ؎ SE) were not significantly different from those of premenopausal patients (110.1 ؎ 10.1 pg/g) (p ‫؍‬ 0.36). The mRNA expression levels of aromatase and sulfatase, determined by a quantitative real-time PCR, were not significantly different between premenopausal and postmenopausal breast cancers, but 17␤-HSD1 mRNA expression levels were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.05). Intratumoral E2/E1 ratios were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.01). These results demonstrate that the increased conversion from E1 to E2 catalyzed by 17␤-HSD1 may play an important role in the maintenance of the intratumoral high E2 levels in postmenopausal patients. © 2001 Wiley-Liss, Inc. Key words: breast cancer; estrogens; aromatase; sulfatase; 17␤-HSD1It has been shown that estrogens play an important role in the growth of hormone-dependent breast cancers. 1,2 In premenopausal women, the major source of estrogens is the ovary, and estrogens produced in the ovary are taken up by tumors and stimulate tumor growth. After menopause, serum estradiol (E2) levels decrease to be as low as about 1/10 of that of premenopausal women. 3,4 However, it has been reported that, even after menopause, intratumoral E2 levels are maintained at high levels that are equivalent to those in premenopausal women. 4 High intratumoral E2 levels in postmenopausal women are supposed to be maintained by the intratumoral biosynthesis of estrogens. [5][6][7] E2 is synthesized in breast cancer tissues through 2 pathways (aromatase and sulfatase pathways). 8 -10 In the aromatase pathway, androstenedione taken up by the tumor from the blood is aromatized into estrone (E1) and then catalyzed into E2 by 17-␤hydrox-ysteroid dehydrogenase type 1 (17-␤ HSD1). [11][12][13] In the sulfatase pathway, estrone sulfate (E1S) taken up by the tumor from the blood is converted into E1 and then catalyzed into E2 by 17␤-HSD1. Several studies have demonstrated the intratumoral expression of these enzymes involved in E2 biosynthesis and stressed the importance of aromatase in the intratumoral biosynthesis of E2. 14 -16 Thus, it is speculated that expression of these enzymes, especially aromatase, is enhanced in postmenopausal women as compared with premenopausal women in order to maintain the high E2 levels in tumors. However, it still remains to be established which enzyme(s) is responsible for the high E2 levels in tumors in postmenopausal women.In the present study, we measured the E2 and E1 levels in breast cancer tissues and investigated the association of the E2 and E1 levels with v...

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The expression levels of the Wilms' tumor gene WT1 were examined in 34 primary thyroid cancers (24 papillary, 5 follicular, 1 anaplastic, and 4 medullary carcinomas), 17 thyroid follicular adenomas, and 6 normal-appearing thyroid tissues using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In 33 of 34 thyroid cancers, the WT1 mRNA was expressed at levels ranging from 5.0 × × × ×10−2 levels (WT1 expression level in K562 leukemic cells was defined as 1.0). The WT1 mRNA expression levels were significantly higher than those in either thyroid follicular adenomas (P < < < <0.001) or normal-appearing thyroid tissues (P < <