Wnt signaling can substitute for estrogen to induce division of ERalpha-positive cells in a mouse mammary tumor model.
The interaction of estrogen with the estrogen receptor (ER, principally ERalpha) induces growth of human breast tumor cells. In contrast, ERalpha-positive cells have been described as non-dividing cells in normal breast (though estrogen stimulation of ERalpha cells directs the division of neighboring cells). However, there is a small sub-population of cells in normal mammary tissue that are ERalpha-positive, that can divide, and therefore share this property with human breast tumor cells. In order to investigate their pattern of growth regulation, we measured the fraction of dividing ERalpha(+) cells during normal growth and compared that to glands stimulated by oncogenic Wnt effectors. First, we found there was no difference between the rate of division of ERalpha(+) cells and ERalpha(-) cells, whether the population was responding to estrogen or Wnt mitogens. The proportion of dividing ERalpha(+) mammary epithelial cells was increased (10x) in response to pregnancy, and similar increases were observed in response to ectopic Wnt signaling. We propose that Wnt signaling can substitute for estrogen to drive total population growth (that includes ERalpha(+) cells). Although the E-ERalpha-derived mitogenic response is situated in a minority of the luminal cells, and the Wnt-LRP5/6-derived mitogenic response is situated in a minority of basal cells, overall, the growth response of the mammary epithelial population is remarkably similar.
Mastroianni
Melissa
M
McArdle Lab for Cancer Research, University of Wisconsin, 1400 University Avenue, Madison 53706, United States.
Kim
Soyoung
S
Kim
Young Chul
YC
Esch
Amanda
A
Wagner
Caroline
C
Alexander
Caroline M
CM
D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
D047628:Estrogen Receptor alpha; D051153:Wnt Proteins