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Vaginal Gene Expression During Treatment With Aromatase Inhibitors
Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
Örebro universitet, Institutionen för hälsovetenskap och medicin. Region Örebro län. Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
Örebro universitet, Institutionen för läkarutbildning. Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden.
Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden.
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2015 (Engelska)Ingår i: Clinical Breast Cancer, ISSN 1526-8209, E-ISSN 1938-0666, Vol. 15, nr 6, s. 527-535.e2Artikel i tidskrift (Refereegranskat) Published
Resurstyp
Text
Abstract [en]

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.

Ort, förlag, år, upplaga, sidor
CIG MEDIA GROUP , 2015. Vol. 15, nr 6, s. 527-535.e2
Nyckelord [en]
Estrogen, Genitourinary symptom of menopause, Microarray, Vagina, Vaginal atrophy
Nationell ämneskategori
Cancer och onkologi
Forskningsämne
Onkologi
Identifikatorer
URN: urn:nbn:se:oru:diva-47079DOI: 10.1016/j.clbc.2015.06.012ISI: 000365190800018PubMedID: 26283501Scopus ID: 2-s2.0-84947022492OAI: oai:DiVA.org:oru-47079DiVA, id: diva2:882562
Forskningsfinansiär
Cancerfonden, CAN 2012/603
Anmärkning

Funding Agencies:

Uppsala-Örebro Regional Research Council

Lions Club International

Percy Falk Foundation

Erik, Karin, and Gösta Selanders Foundation

Tillgänglig från: 2015-12-15 Skapad: 2015-12-15 Senast uppdaterad: 2018-07-02Bibliografiskt granskad

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Baumgart, JulianeNilsson, Kerstin

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Institutionen för hälsovetenskap och medicinRegion Örebro länInstitutionen för läkarutbildning
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Clinical Breast Cancer
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