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Vaginal Gene Expression During Treatment With Aromatase Inhibitors.
Kallak, Theodora Kunovac; Baumgart, Juliane; Nilsson, Kerstin; Åkerud, Helena; Poromaa, Inger Sundström; Stavreus-Evers, Anneli.
Afiliación
  • Kallak TK; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. Electronic address: theodora.kunovac_kallak@kbh.uu.se.
  • Baumgart J; Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden; The School of Health and Medical Sciences; Örebro University, Örebro, Sweden.
  • Nilsson K; Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health and Medicine, Örebro University, Örebro, Sweden.
  • Åkerud H; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
  • Poromaa IS; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
  • Stavreus-Evers A; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Clin Breast Cancer ; 15(6): 527-535.e2, 2015 Dec.
Article en En | MEDLINE | ID: mdl-26283501
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vagina / Neoplasias de la Mama / Antineoplásicos Hormonales / Inhibidores de la Aromatasa / Transcriptoma Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Aspecto: Patient_preference Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Clin Breast Cancer Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vagina / Neoplasias de la Mama / Antineoplásicos Hormonales / Inhibidores de la Aromatasa / Transcriptoma Tipo de estudio: Observational_studies / Prevalence_studies / Risk_factors_studies Aspecto: Patient_preference Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Clin Breast Cancer Asunto de la revista: NEOPLASIAS Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos