Oestrogen receptor-beta signalling protects against transplanted skin tumour growth in the mouse.
We have reported previously that a deficiency in signalling by the non-classical oestrogen receptor-beta (Er-beta) exacerbates immunosuppression by UV radiation in the mouse. Because photoimmune suppression is a risk factor for skin cancer development, we hypothesize that Er-beta deficiency will promote skin tumour growth. Therefore we have blocked Er signalling pharmacologically in the Skh:hr-1 hairless mouse by topical treatments with the Er antagonist ICI 182,780, and genetically in haired mice by using the specific Er-beta knockout mouse (targeted mutation of the Er-beta), and examined the growth rate of 3 transplantable skin tumour cell lines in their syngeneic host mice. Two UV-induced squamous cell carcinoma (SCC) cell lines transplanted into the Skh:hr-1 recipients were found to have regressor qualities that were delayed by prior immunosuppressive solar-simulated UV (SSUV) irradiation. For the T79 SCC, regression was significantly further delayed by combined pretreatment with SSUV+ICI 182,780, and the diameters of the surviving tumours were slightly larger. For the KL3.0 SCC, both SSUV and combined SSUV+ICI 182,780 pretreatments completely inhibited tumour regression, and resulted in significantly greater tumour diameters than in unirradiated recipient mice. In heterozygous Er-beta deficient mice (Er-beta+/-), the B16/F10 melanoma grew progressively and significantly faster than in the wild type control mice (C57BL/6), and growth rate was accelerated by prior SSUV irradiation. Homozygous Er-beta-/- mice supported the most rapid B16/F10 growth that was further accelerated by prior SSUV irradiation. Therefore Er signalling, specifically by Er-beta, has a natural endogenous protective role against skin tumour growth, probably mediated via immunological pathways.
Cho
Jun-Lae
JL
Faculty of Veterinary Science, University of Sydney, McMaster Building B14, Sydney, New South Wales 2006, Australia.
Allanson
Munif
M
Reeve
Vivienne E
VE
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D003877:Dermatitis, Contact / Q000276:immunology / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D055786:Gene Knockout Techniques; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects
D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D004958:Estradiol