Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment.

MONTERO GIRARD G, VANZULLI SI, CERLIANI JP, BOTTINO MC, BOLADO J, VELA J, BECU-VILLALOBOS D, BENAVIDES F, GUTKIND S, PATEL V, MOLINOLO A, LANARI C.

BREAST CANCER RESEARCH

Año: 2007 vol. 9 p. 1 - 22

Medroxyprogesterone acetate (MPA) induces estrogen (ER) and progesterone receptor (PR) positive ductal mammary carcinomas in BALB/c mice. To corroborate preliminary results indicating wide differences in hormone responses of the mammary glands between C57BL/6 and BALB/c, we studied the differential carcinogenic effect of MPA, the morphological changes induced by progestins, and ER and PR receptor expression. Furthermore,  we carried out epithelial cell transplantation experiments to evaluate a possible role of the stroma. MPA failed to induce mammary carcinomas or significant morphological changes in the mammary glands of C57BL/6 mice. Basal expression of ER alpha (ERa) and PR isoform A was surprisingly much higher in BALB/c than in C57BL/6 mammary glands and both receptors were down-regulated in progestin-treated BALB/c mice (p<0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ERb expression followed a similar trend. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice pretreated with hormones abolished the mammary gland morphological differences between strains. We conclude that this pair of strains constitutes an excellent model to study stromal-parenchymal interactions which determine breast cancer susceptibility.