Lack of ductal development in the absence of functional estrogen receptor alpha delays mammary tumor formation induced by transgenic expression of ErbB2/neu

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2002-05, Vol.62 (10), p.2798-2805
Main Authors: Hewitt, Sylvia Curtis, Bocchinfuso, Wayne P, Zhai, Jun, Harrell, Chuck, Koonce, Linwood, Clark, James, Myers, Page, Korach, Kenneth S
Format: Article
Language:English
Subjects:
Animals
Estrogen Receptor alpha
Female
Male
Mammary Neoplasms, Experimental - genetics
Mammary Neoplasms, Experimental - metabolism
Mammary Neoplasms, Experimental - pathology
Mammary Neoplasms, Experimental - virology
Mammary Tumor Virus, Mouse - genetics
Mice
Mice, Knockout
Mice, Transgenic
Progesterone - metabolism
Receptor, ErbB-2 - biosynthesis
Receptor, ErbB-2 - genetics
Receptors, Estrogen - deficiency
Receptors, Estrogen - genetics
Receptors, Estrogen - physiology
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Summary: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.
ISSN:0008-5472
1538-7445