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Photochem Photobiol Sci. 2010 Apr;9(4):608-14. doi: 10.1039/b9pp00168a.

Oestrogen receptor-beta signalling protects against transplanted skin tumour growth in the mouse.

Author information

1
Faculty of Veterinary Science, University of Sydney, McMaster Building B14, Sydney, New South Wales 2006, Australia.

Abstract

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.

PMID:
20354658
DOI:
10.1039/b9pp00168a
[Indexed for MEDLINE]

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