Estrogenic Regulation of Host Immunity against an Estrogen Receptor-Negative Human Breast Cancer Export

@article{citeulike:4069231, abstract = {Purpose: The risk of developing breast cancer is positively correlated with exposure to increased levels of estrogen and/or an increased duration of estrogen exposure. Many different mechanisms have been proposed to explain the association of estrogens with breast cancer risk; however, the well-documented immune modulatory properties of estrogen have received little attention. In part, this is due to a lack of suitable models for studying this relationship. Experimental Design: We have developed an animal model using estrogen receptor (ER)-negative human breast cancer cell line, MDA-MB-468, xenografted into severe combined immunodeficient (SCID) mice. We also generated the ER-{alpha} knockout (ER-{alpha}KO) mice on the SCID background and then tested the ability of 17{beta}-estradiol to stimulate growth of xenografted ER-negative human breast cancer tumors in wild-type and ER-{alpha}KO SCID mice. We quantified vascularization of tumors, macrophage recruitment to the tumor site by immunocytochemistry, and inflammatory cytokine production. Results: We show that estrogen treatment of C57BL/6/SCID mice promotes the growth of xenografted ER-negative tumors in wild-type mice and this estrogen-induced tumor growth is abrogated in ER-{alpha}KO mice. Tumor neovascularization of estrogen-treated mice was unchanged versus control; however, estrogen treatment of the C57BL/6/SCID host suppressed macrophage recruitment to and inflammatory cytokine production at the tumor site. Conclusions: These data are consistent with estrogen modulation of the inflammatory response as a contributing factor in estrogen-stimulated growth of an ER-negative tumor. This effect on the host innate immune response was mediated by ER-{alpha}. 10.1158/1078-0432.CCR-05-1117}, author = {Curran, Edward M. and Judy, Barbara M. and Duru, Ngozi A. and Wang, Hui-Qun and Vergara, Leoncio A. and Lubahn, Dennis B. and Estes, Mark D.}, citeulike-article-id = {4069231}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-05-1117}, citeulike-linkout-1 = {http://clincancerres.aacrjournals.org/cgi/content/abstract/12/19/5641?rss=1}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17000652}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17000652}, comment = {Estrogen regulates innate immunity in estrogen-receptor-negative breast cancer.}, day = {1}, doi = {10.1158/1078-0432.CCR-05-1117}, journal = {Clin Cancer Res}, keywords = {breast, cancer, check, defref, estrogen-immune, estrogen-immunomodulation, thelist}, month = {October}, number = {19}, pages = {5641--5647}, posted-at = {2009-02-19 01:41:01}, priority = {2}, title = {Estrogenic Regulation of Host Immunity against an Estrogen Receptor-Negative Human Breast Cancer}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-05-1117}, volume = {12}, year = {2006} }

TY - JOUR ID - citeulike:4069231 L3 - citeulike-article-id:4069231 N2 - Purpose: The risk of developing breast cancer is positively correlated with exposure to increased levels of estrogen and/or an increased duration of estrogen exposure. Many different mechanisms have been proposed to explain the association of estrogens with breast cancer risk; however, the well-documented immune modulatory properties of estrogen have received little attention. In part, this is due to a lack of suitable models for studying this relationship. Experimental Design: We have developed an animal model using estrogen receptor (ER)-negative human breast cancer cell line, MDA-MB-468, xenografted into severe combined immunodeficient (SCID) mice. We also generated the ER-{alpha} knockout (ER-{alpha}KO) mice on the SCID background and then tested the ability of 17{beta}-estradiol to stimulate growth of xenografted ER-negative human breast cancer tumors in wild-type and ER-{alpha}KO SCID mice. We quantified vascularization of tumors, macrophage recruitment to the tumor site by immunocytochemistry, and inflammatory cytokine production. Results: We show that estrogen treatment of C57BL/6/SCID mice promotes the growth of xenografted ER-negative tumors in wild-type mice and this estrogen-induced tumor growth is abrogated in ER-{alpha}KO mice. Tumor neovascularization of estrogen-treated mice was unchanged versus control; however, estrogen treatment of the C57BL/6/SCID host suppressed macrophage recruitment to and inflammatory cytokine production at the tumor site. Conclusions: These data are consistent with estrogen modulation of the inflammatory response as a contributing factor in estrogen-stimulated growth of an ER-negative tumor. This effect on the host innate immune response was mediated by ER-{alpha}. 10.1158/1078-0432.CCR-05-1117 IS - 19 JF - Clin Cancer Res EP - 5647 TI - Estrogenic Regulation of Host Immunity against an Estrogen Receptor-Negative Human Breast Cancer VL - 12 SP - 5641 KW - breast KW - cancer KW - check KW - defref KW - estrogen-immune KW - estrogen-immunomodulation KW - thelist N1 - Estrogen regulates innate immunity in estrogen-receptor-negative breast cancer. AU - Curran, Edward AU - Judy, Barbara AU - Duru, Ngozi AU - Wang, Hui-Qun AU - Vergara, Leoncio AU - Lubahn, Dennis AU - Estes, Mark PY - 2006/10/01/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-05-1117 ER -