Tamoxifen induction of angiogenic factor expression in endometrium.
Tamoxifen is the current therapy of choice for patients with oestrogen receptor positive breast cancer, and it is currently under evaluation as a prophylactic for women at high risk of developing the disease. However, tamoxifen is also known to induce proliferative changes in the endometrium increasing the risk of developing endometrial hyperplasia, polyps and carcinoma. Angiogenesis is an intimate part of this process. For this reason, we have examined the expression of several well characterized angiogenic factors, namely, acidic and basic fibroblast growth factor, thymidine phosphorylase, vascular endothelial growth factor and adrenomedullin in both normal and tamoxifen exposed pre- and postmenopausal endometrium. Vascular density and endothelial proliferation index were also quantified. We found increased expression of acidic and basic fibroblast growth factor and adrenomedullin after treatment with tamoxifen mainly in premenopausal tissue. Vascular density was significantly increased in pre- but not post-menopausal endometrium (P=0.0018) following tamoxifen treatment. These results support the notion that angiogenesis is integral to the response to tamoxifen exposure, and is a potential target with which to block these side effects of tamoxifen.
Hague
S
S
Nuffield Department of Obstetrics and Gynaecology, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Manek
S
S
Oehler
M K
MK
MacKenzie
I Z
IZ
Bicknell
R
R
Rees
M C P
MC
D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D004717:Endometrium / Q000098:blood supply* / Q000187:drug effects; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000032:analysis; D017698:Postmenopause; D017697:Premenopause; D013629:Tamoxifen / Q000009:adverse effects* / Q000494:pharmacology
D018931:Antineoplastic Agents, Hormonal; D010455:Peptides; D013629:Tamoxifen; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D053607:Adrenomedullin