Abstract
Increased intratumoral expression of aromatase, the key enzyme for estrogen biosynthesis, is predicted to be of critical importance in the development of breast cancer. Recently, several germline rearrangements at 15q21 have been shown to cause overexpression of the aromatase gene CYP19A1 and resulting aromatase excess syndrome. To determine whether submicroscopic genomic rearrangements at 15q21 are involved in aromatase overexpression in breast cancer tissues, we investigated copy-number alterations in genomic DNA obtained from 44 tumor samples. Comparative genomic hybridization analysis identified no deletion or duplication at 15q21 in the 44 samples. These results, in conjunction with previous data, indicate that aromatase overexpression in breast cancer tissues is likely to result from a promoter switch of CYP19A1 and/or accumulation of CYP19A1-expressing cells, rather than from cryptic transactivation of CYP19A1 because of genomic rearrangements at 15q21.
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Abbreviations
- AEXS:
-
Aromatase excess syndrome
- CGH:
-
Comparative genomic hybridization
References
Bulun SE, Lin Z, Imir G, Amin S, Demura M, Yilmaz B, et al. Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacol Rev. 2005;57:359–83.
Kulendran M, Salhab M, Mokbel K. Oestrogen-synthesising enzymes and breast cancer. Anticancer Res. 2009;29:1095–109.
Bulun SE, Chen D, Lu M, Zhao H, Cheng Y, Demura M, et al. Aromatase excess in cancers of breast, endometrium and ovary. J Steroid Biochem Mol Biol. 2007;106:81–96.
Sasano H, Miki Y, Nagasaki S, Suzuki T. In situ estrogen production and its regulation in human breast carcinoma: from endocrinology to intracrinology. Pathol Int. 2009;59:777–89.
Bulun SE, Lin Z, Zhao H, Lu M, Amin S, Reierstad S, et al. Regulation of aromatase expression in breast cancer tissue. Ann N Y Acad Sci. 2009;1155:121–31.
Demura M, Martin RM, Shozu M, Sebastian S, Takayama K, Hsu WT, et al. Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene. Hum Mol Genet. 2007;16:2529–41.
Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K, et al. Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene. N Engl J Med. 2003;348:1855–65.
Fukami M, Shozu M, Soneda S, Kato F, Inagaki A, Takagi H, et al. Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants. J Clin Endocrinol Metab. 2011;96:E1035–43.
Naoi Y, Kishi K, Tanei T, Tsunashima R, Tominaga N, Baba Y, et al. Development of 95-gene classifier as a powerful predictor of recurrences in node-negative and ER-positive breast cancer patients. Breast Cancer Res Treat. 2011;128:633–41.
Fridlyand J, Snijders AM, Ylstra B, Li H, Olshen A, Segraves R, et al. Breast tumor copy number aberration phenotypes and genomic instability. BMC Cancer. 2006;6:96.
Khan SI, Zhao J, Khan IA, Walker LA, Dasmahapatra AK. Potential utility of natural products as regulators of breast cancer-associated aromatase promoters. Reprod Biol Endocrinol. 2011;9:91.
Bulun SE, Price TM, Aitken J, Mahendroo MS, Simpson ER. A link between breast cancer and local estrogen biosynthesis suggested by quantification of breast adipose tissue aromatase cytochrome P450 transcripts using competitive polymerase chain reaction after reverse transcription. J Clin Endocrinol Metab. 1993;77:1622–8.
Bulun SE, Simpson ER. Breast cancer and expression of aromatase in breast adipose tissue. Trends Endocrinol Metab. 1994;5:113–20.
Acknowledgments
This work was supported by the Grant-in-Aid for Scientific Research on Innovative Areas (22132004) from the Ministry of Education, Culture, Sports, Science and Technology, by the Grant-in-Aid for Scientific Research (B) (23390249) from the Japan Society for the Promotion of Science, by the Grant for Research on Intractable Diseases from the Ministry of Health, Labor and Welfare, and by the Grants from National Center for Child Health and Development, from Takeda foundation, and from Daiichi-Sankyo Foundation of Life Science.
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The authors declare that no conflict of interests exists.
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Fukami, M., Suzuki, J., Nakabayashi, K. et al. Lack of genomic rearrangements involving the aromatase gene CYP19A1 in breast cancer. Breast Cancer 21, 382–385 (2014). https://doi.org/10.1007/s12282-013-0471-5
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DOI: https://doi.org/10.1007/s12282-013-0471-5