THYROID HORMONE REGULATES CRABP1 IN MOUSE MAMMARY GLAND ADIPOSE STROMAL CELLS

Background: The prognosis of breast cancer is strongly influenced by the developmental stage of the breast when the tumor is diagnosed. Pregnancy-associated breast cancers, cancers diagnosed during pregnancy, lactation, or in the first postpartum year, are typically found at an advanced stage, are more aggressive and have a poorer prognosis. Adipose stromal cell (ASC) remodeling is responsible for these cancers. The amount of the gland occupied by adipose tissue fluctuates during pregnancy and lactation such that the lactating gland has the least amount of adipose. Crabp1 is present during lactation and functions to prevent lipid accumulation. We have also shown that it is able to promote pregnancy associated breast cancer. The upstream regulators of crabp1 in the normal and diseased mammary gland remain unknown however. In this study we aim to determine if thyroid hormone regulates crabp1 gene expression. Methods: We isolated ASCs from mice at each stage of mammary gland development and cultured the cells in the presence and absence of thyroid hormone. We performed qPCR and Western blotting to determine the levels of crabp1 in each stage of development.Results: Our data suggest that the stage of mammary gland development dictates the amount of crapb1 levels in response to thyroid hormone treatment. Crabp1 levels do not change in ASC-Nulliparous or ASC-Regressed cells. In contrast, crabp1 levels are increased in ASC-Pregnant after only 24 hours of thyroid hormone treatment while ASC-Involuting cells have an increase in crabp1 levels only after 7 days of treatment. Conclusions: Thyroid hormone may be a key regulator of crabp1 expression in the mammary adipose stroma. Its promoter contains a thyroid hormone response element and thyroid hormone levels increase at partuition. In fact it is required for lactation. Thus it may be the signal in the mammary gland to increase crabp1 levels to remodel the adipose tissue at lactation.