Vaginal Gene Expression During Treatment With Aromatase Inhibitors.
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.


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.


CONCLUSIONS
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.
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden. Electronic address: theodora.kunovac_kallak@kbh.uu.se.
Theodora Kunovac
TK
Kallak
Department of Obstetrics and Gynecology, Örebro University Hospital, Örebro, Sweden; The School of Health and Medical Sciences; Örebro University, Örebro, Sweden.
Juliane
J
Baumgart
Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health and Medicine, Örebro University, Örebro, Sweden.
Kerstin
K
Nilsson
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Helena
H
Åkerud
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Inger Sundström
IS
Poromaa
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Anneli
A
Stavreus-Evers
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001141:Aromatase / Q000096:biosynthesis; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects*; D014621:Vagina / Q000187:drug effects* / Q000201:enzymology
D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D001141:Aromatase
Estrogen; Genitourinary symptom of menopause; Microarray; Vagina; Vaginal atrophy