PDF
ePub
Citation
Print
Abstract
Purpose
The 17β-hydroxysteroid dehydrogenases(17HSDs) play an important role in the regulation of the physiologic activities of sex steroid hormones. The predominance of 17HSD type 1 in the malignant breast tissue could increase the estrogen-dependent proliferation and stimulate the cancer progression. On the other hand, the oxidative 17HSD type 2 may protect the normal breast cells from an excessive estradiol effect. To identify the role of 17HSD type 2 in the carcinogenesis of breast cancer, we investigate the mutation of 17HSD type 2 in 35 breast cancers.
Methods
We analyzed the entire coding region of the 17 HSD type 2 gene for detection of the somatic mutations in 35 invasive ductal carcinomas of the breast by polymerase chain reaction, single strand conformation polymorphism, and DNA sequencing.
Results
We found one missense mutation in exon 6(2.86%). It revealed the CCT→CTT (Pro→Leu) transition type at codon 262 in exon 6.
Conclusion
In present study, we found only a mutation of the 17β-HSD type 2 gene in breast cancer and could not demonstrate the direct relationship between the mutation of the 17β-HSD type 2 gene and the development of breast cancer. These results suggest that the mutation of 17HSD type 2 doesn't play a major role in the development of breast cancer.
References
1. Peltoketo H, Vihko P, Vihko R. Regulation of estrogen action: role of 17 beta-hydroxysteroid dehydrogenases. Vitam Horm. 1999. 55:353–398.
2. Adamski J, Jakob FJ. A guide to 17beta-hydroxysteroid dehydrogenases. Mol Cell Endocrinol. 2001. 171:1–4.
3. Peltoketo H, Isomaa V, Maentausta O, Vihko R. Complete amino acid sequence of human placental 17 beta-hydroxysteroid dehydrogenase deduced from cDNA. FEBS Lett. 1988. 239:73–77.
4. Luu The V, Labrie C, Zhao HF, Couet J, Lachance Y, Simard J, et al. Characterization of cDNAs for human estradiol 17 beta-dehydrogenase and assignment of the gene to chromosome 17: evidence of two mRNA species with distinct 5'termini in human placenta. Mol Endocrinol. 1989. 3:1301–1309.
5. Miettinen MM, Mustonen MV, Poutanen MH, Isomaa VV, Vihko RK. Human 17 beta-hydroxysteroid dehydrogenase type 1 and type 2 isoenzymes have opposite activities in cultured cells and characteristic cell- and tissue-specific expression. Biochem J. 1996. 314:839–845.
6. Vermeulen A, Deslypere JP, Paridaens R, Leclercq G, Roy F, Heuson JC, et al. 17 beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. Eur J Cancer Clin Oncol. 1986. 22:515–525.
7. Wu L, Einstein M, Geissler WM, Chan HK, Elliston KO, Andersson S. Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity. J Biol Chem. 1993. 268:12964–12969.
8. Casey ML, MacDonald PC, Andersson S. 17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium. J Clin Invest. 1994. 94:2135–2141.
9. Sasano H, Frost AR, Saitoh R, Harada N, Poutanen M, Vihko R, et al. Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma. J Clin Endocrinol Metab. 1996. 81:4042–4046.
10. Vihko P, Harkonen P, Soronen P, Torn S, Herrala A, Kurkela R, et al. 17 beta-hydroxysteroid dehydrogenases--their role in pathophysiology. Mol Cell Endocrinol. 2004. 215:83–88.
11. Lee JY, Dong SM, Kim SY, Yoo NJ, Lee SH, Park WS. A simple, precise and economical microdissection technique for analysis of genomic DNA from archival tissue sections. Virchows Arch. 1998. 433:305–309.
12. Platet N, Cathiard AM, Gleizes M, Garcia M. Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion. Crit Rev Oncol Hematol. 2004. 51:55–67.
13. Speirs V, Green AR, Atkin SL. Activity and gene expression of 17beta-hydroxysteroid dehydrogenase type I in primary cultures of epithelial and stromal cells derived from normal and tumourous human breast tissue: the role of IL-8. J Steroid Biochem Mol Biol. 1998. 67:267–274.
14. Vihko P, Harkonen P, Oduwole O, Torn S, Kurkela R, Porvari K, et al. 17 beta-hydroxysteroid dehydrogenases and cancers. J Steroid Biochem Mol Biol. 2002. 83:119–122.
15. Gunnarsson C, Hellqvist E, Stal O. 17beta-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer. Br J Cancer. 2005. 92:547–552.
16. Mustonen MV, Poutanen MH, Kellokumpu S, de Launoit Y, Isomaa VV, Vihko RK, et al. Mouse 17 beta-hydroxysteroid dehydrogenase type 2 mRNA is predominantly expressed in hepatocytes and in surface epithelial cells of the gastrointestinal and urinary tracts. J Mol Endocrinol. 1998. 20:67–74.
17. Lin YW, Lee IN, Chen CH, Huang GT, Lee HS, Lee PH, et al. Deletion mapping of chromosome 16q24 in hepatocellular carcinoma in Taiwan and mutational analysis of the 17-beta-HSD gene localized to the region. Int J Cancer. 2001. 93:74–79.
18. Mannermaa A, Peltoketo H, Winqvist R, Ponder BA, Kiviniemi H, Easton DF, et al. Human familial and sporadic breast cancer: analysis of the coding regions of the 17 beta-hydroxysteroid dehydrogenase 2 gene (EDH17B2) using a single-strand conformation polymorphism assay. Hum Genet. 1994. 93:319–324.
XML Download