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 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.
Hewitt
Sylvia Curtis
SC
Receptor Biology Section, Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences/NIH, Research Triangle Park, NC 27709, USA.
Bocchinfuso
Wayne P
WP
Zhai
Jun
J
Harrell
Chuck
C
Koonce
Linwood
L
Clark
James
J
Myers
Page
P
Korach
Kenneth S
KS
D000818:Animals; D047628:Estrogen Receptor alpha; D005260:Female; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011374:Progesterone / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D047628:Estrogen Receptor alpha; D011374:Progesterone; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen