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  • Title: Lack of ductal development in the absence of functional estrogen receptor alpha delays mammary tumor formation induced by transgenic expression of ErbB2/neu.
    Author: Hewitt SC, Bocchinfuso WP, Zhai J, Harrell C, Koonce L, Clark J, Myers P, Korach KS.
    Journal: Cancer Res; 2002 May 15; 62(10):2798-805. PubMed ID: 12019156.
    Abstract:
    Expression of the mouse mammary tumor virus (MMTV) neu/erbB2 transgene in mice induces mammary tumors. To examine the effect of removing estrogen receptor alpha (ERalpha) signaling on the ability of an MMTV-neu/erbB2 transgene to induce mammary tumors, the neu transgene was expressed in the ERalpha knockout (alphaERKO) mouse, which lacks functional ERalpha. MMTV-neu females that lacked ERalpha still developed mammary tumors; however, tumor onset was significantly delayed. This study indicates that ERalpha is not required for mammary tumor induction by overexpression of neu/erbB2, but plays a role in the rate of tumor onset. The removal of ovarian steroid by ovariectomy in adults did not alter the onset rate. In contrast, prepubertal ovariectomy, which arrested mammary epithelial development, significantly delayed onset. In addition, manipulations that increase progesterone also accelerate the tumor onset, indicating the slower onset in the alphaERKO is primarily attributable to the anovulatory phenotype resulting in lack of progesterone stimulation and a decreased abundance of target cells in the alphaERKO mammary gland.
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