Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy

Ghimenti,Chiara; Mello-Grand,Maurizia; Grosso,Enrico; Scatolini,Maria; Regolo,Lea; Zambelli,Alberto; Chiorino,Giovanna

doi:10.3892/etm.2012.878

March 2013 Volume 5 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

March 2013 Volume 5 Issue 3

Full Size Image

Article

Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy

Authors:
- Chiara Ghimenti
- Maurizia Mello-Grand
- Enrico Grosso
- Maria Scatolini
- Lea Regolo
- Alberto Zambelli
- Giovanna Chiorino
View Affiliations / Copyright

Affiliations: Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia Valenta, Biella, Italy, Unit of Senology, IRCCS Fondazione ‘Salvatore Maugeri’, Pavia, Italy, Unit of Medical Oncology, IRCCS Fondazione ‘Salvatore Maugeri’, Pavia, Italy
Pages: 902-906
|
Published online on: December 24, 2012

https://doi.org/10.3892/etm.2012.878
Expand metrics +

Abstract

Aromatase inhibitors (AIs), such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, ~20% of patients with hormone receptor‑positive breast tumors treated with anastrozole do not respond and it remains impossible to accurately predict sensitivity. Since polymorphisms in the aromatase gene may influence the response to inhibitory drugs, we evaluated the presence of rs6493497 and rs7176005 polymorphisms (mapping in the 5'‑flanking region of the CYP19A1 gene coding for the aromatase protein) in a cohort of 37 patients with postmenopausal breast cancer who received three-month neoadjuvant treatment with anastrozole. We then investigated any association of the polymorphisms with changes in aromatase mRNA expression change and/or response to treatment. We also analyzed five miRNAs computationally predicted to target aromatase, to observe any association between their expression and sensitivity to anastrozole. Three samples carried the two polymorphisms and the remaining samples were wild-type for both, however, no association with response or with aromatase mRNA basal expression level or expression difference after therapy was observed. Polymorphic samples that were resistant to anastrozole showed no change or decrease in aromatase expression following AI treatment, whereas an increase in expression was observed for the polymorphic responsive samples. No statistically significant correlation was observed between miRNA and aromatase mRNA expression, or with response to anastrozole neoadjuvant treatment. These data indicate that the polymorphisms analyzed are not involved in aromatase activity and that other epigenetic mechanisms may regulate aromatase protein expression.

View Figures

View References

1.	Yue W, Wang JP, Hamilton CJ, et al: In situ aromatization enhances breast tumor estradiol levels and cellular proliferation. Cancer Res. 58:927–932. 1998.PubMed/NCBI
2.	Brueggemeier RW, Hackett JC and Diaz-Cruz ES: Aromatase inhibitors in the treatment of breast cancer. Endocr Rev. 26:331–345. 2005. View Article : Google Scholar : PubMed/NCBI
3.	Wang L, Ellsworth KA, Moon I, et al: Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to neoadjiuvant therapy with aromatase inhibitors. Cancer Res. 70:319–328. 2010. View Article : Google Scholar : PubMed/NCBI
4.	Shibahara Y, Miki Y, Onodera Y, et al: Aromatase inhibitor treatment of breast cancer cells increases the expression of let-7f, a microRNA targeting CYP19A1. J Pathol. 227:357–366. 2012. View Article : Google Scholar : PubMed/NCBI
5.	Ghimenti C, Mello Grand M, Regolo L, Zambelli A and Chiorino G: Absence of K303R estrogen receptor-α mutation in breast cancer patients with different response to aromatase inhibitor anastrozole neoadjuvant treatment. Exp Ther Med. 1:939–942. 2010.
6.	Therasse P, Arbuck SG, Eisenhauer EA, et al: New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 92:205–216. 2000. View Article : Google Scholar
7.	Mello-Grand M, Singh V, Ghimenti C, et al: Gene expression profiling and prediction of response to hormonal neoadjuvant treatment with anastrozole in surgically resectable breast cancer. Breast Cancer Res Treat. 121:399–411. 2010. View Article : Google Scholar : PubMed/NCBI
8.	Xu S, Linher-Melville K, Yang BB, et al: Micro-RNA378 (miR-378) regulates ovarian estradiol production by targeting aromatase. Endocrinology. 152:3941–3951. 2011. View Article : Google Scholar : PubMed/NCBI
9.	Colomer R, Monzo M, Tusquets I, et al: A single-nucleotide polymorphism in the aromatase gene is associated with the efficacy of the aromatase inhibitor letrozole in advanced breast carcinoma. Clin Cancer Res. 14:811–816. 2008. View Article : Google Scholar : PubMed/NCBI
10.	Garcia-Casado Z, Guerrero-Zotano A, Llombart-Cussac A, et al: A polymorphism at the 3′-UTR region of the aromatase gene defines a subgroup of postmenopusal breast cancer patients with poor response to neoadjuvant letrozole. BMC Cancer. 10:362010.
11.	Park IH, Lee YS and Lee KS: Single nucleotide polymorphisms of CYP19A1 predict clinical outcomes and adverse events associated with letrozole in patients with metastatic breast cancer. Cancer Chemother Pharmacol. 68:1263–1271. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy

This article is mentioned in:

Abstract

Related Articles