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

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Abstract

We have reported previously that a deficiency in signalling by the non-classical oestrogen receptor-β (Er-β) exacerbates immunosuppression by UV radiation in the mouse. Because photoimmune suppression is a risk factor for skin cancer development, we hypothesize that Er-β deficiency will promote skin tumour growth. Therefore we have blocked Ersignalling pharmacologically in the Skh:hr-1 hairless mouse by topical treatments with the Erantagonist ICI 182,780, and genetically in haired mice by using the specific Er-β knockout mouse (targeted mutation of the Er-β), 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-β deficient mice (Er-β+/−), 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-β−/− mice supported the most rapid B16/F10 growth that was further accelerated by prior SSUV irradiation. Therefore Ersignalling, specifically by Er-β, has a natural endogenous protective role against skin tumour growth, probably mediated via immunological pathways.

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Authors and Affiliations

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

    Jun-Lae Cho, Munif Allanson & Vivienne E. Reeve

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  1. Jun-Lae Cho
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  2. Munif Allanson
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  3. Vivienne E. Reeve
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Correspondence to Vivienne E. Reeve.

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Cho, JL., Allanson, M. & Reeve, V.E. Oestrogen receptor-β signalling protects against transplanted skin tumour growth in the mouse. Photochem Photobiol Sci 9, 608–614 (2010). https://doi.org/10.1039/b9pp00168a

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