Vaginal gene expression during treatment with aromatase inhibitors
2015 (English)In: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 15, no 6, 527-535 p.Article in journal (Refereed) Published
Vaginal gene expression in aromatase inhibitor-treated women was compared with postmenopausal control women treated with vaginal estrogen therapy. Vaginal tissue from aromatase inhibitor-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion, and associated with vaginal discomfort. The presence of vaginal aromatase suggests that this is the result of local and systemic aromatase inhibition. Background: Aromatase inhibitor (AI) treatment suppresses estrogen biosynthesis and causes genitourinary symptoms of menopause such as vaginal symptoms, ultimately affecting the quality of life for many postmenopausal women with breast cancer. Thus, the aim of this study was to examine vaginal gene expression in women during treatment with AIs compared with estrogen-treated women. The secondary aim was to study the presence and localization of vaginal aromatase. Patients and Methods: Vaginal biopsies were collected from postmenopausal women treated with AIs and from age-matched control women treated with vaginal estrogen therapy. Differential gene expression was studied with the Affymetrix Gene Chip Gene 1.0 ST Array (Affymetrix Inc, Santa Clara, CA) system, Ingenuity pathway analysis, quantitative real-time polymerase chain reaction, and immunohistochemistry. Results: The expression of 279 genes differed between the 2 groups; AI-treated women had low expression of genes involved in cell differentiation, proliferation, and cell adhesion. Some differentially expressed genes were found to interact indirectly with the estrogen receptor alpha. In addition, aromatase protein staining was evident in the basal and the intermediate vaginal epithelium layers, and also in stromal cells with a slightly stronger staining intensity found in AI-treated women. Conclusion: In this study, we demonstrated that genes involved in cell differentiation, proliferation, and cell adhesion are differentially expressed in AI-treated women. The expression of vaginal aromatase suggests that this could be the result of local and systemic inhibition of aromatase. Our results emphasize the role of estrogen for vaginal cell differentiation and proliferation and future drug candidates should be aimed at improving cell differentiation and proliferation. (C) 2015 Elsevier Inc. All rights reserved.
Place, publisher, year, edition, pages
2015. Vol. 15, no 6, 527-535 p.
Estrogen; Genitourinary symptom of menopause; Microarray; Vagina; Vaginal atrophy
Obstetrics, Gynecology and Reproductive Medicine
IdentifiersURN: urn:nbn:se:uu:diva-245413DOI: 10.1016/j.clbc.2015.06.012ISI: 000365190800018PubMedID: 26283501OAI: oai:DiVA.org:uu-245413DiVA: diva2:791163
FunderSwedish Cancer Society, CAN 2012/603