Estrogen decreases chemokine levels in murine mammary tissue: implications for the regulatory role of MIP-1 alpha and MCP-1/JE in mammary tumor formation.
Estrogen contributes to the development of breast cancer through mechanisms that are not completely understood. Estrogen influences the function of immune effector cells, primarily through alterations in cytokine expression. Chemokines are proinflammatory cytokines that attract various immune cells to the site of tissue injury or inflammation, and activate many cell types, including T lymphocytes and monocytes. As an initial step toward ultimately determining whether regulation of chemokine expression and/or biological activity by estrogen could potentially be a contributing factor to the development and progression of mammary tumors, we evaluated the effect of estrogen on the expression of specific chemokines in murine mammary tissue. We also evaluated whether exposure of female mice to various chemokines could alter the growth of mammary tumors in the presence of estrogen. We report here that estrogen significantly decreases levels of the chemokines MIP-1alpha and MCP-1/JE in murine mammary tissue. Co-treatment with 4-hydroxytamoxifen partially reverses the suppressive effect of estrogen on MIP-1alpha levels. Estrogen increases the growth of CCL- 51 cell-based tumors in the mammary glands of female mice. Co-treatment with the chemokine MIP-1alpha or MCP- 1/JE substantially decreases the ability of estrogen to stimulate the formation of CCL-51 cell-based tumors. Our results show that estrogen might influence the bioactivity of specific chemokines through alteration of chemokine expression in mammary tissue, and further suggest that decreases in murine chemokines evoked by estrogen exposure could contribute to the promotion of mammary tumor growth.
Fanti
Peter
P
Department of Biology, Canisius College, 304 Health Science Center, 2001 Main Street, Buffalo, NY 14208, USA
Nazareth
Michael
M
Bucelli
Robert
R
Mineo
Michael
M
Gibbs
Kathleen
K
Kumin
Michael
M
Grzybek
Kevin
K
Hoeltke
Janice
J
Raiber
Lisa
L
Poppenberg
Kristin
K
Janis
Kelly
K
Schwach
Catherine
C
Aronica
Susan M
SM
D000818:Animals; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D051379:Mice
D018932:Chemokine CCL2; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018925:Chemokines; D004967:Estrogens; D019402:Macrophage Inflammatory Proteins