ESR1 and cancer: To do so, we injected the ERα-negative cancer cells B16K1 to immunocompetent ovariectomized mice deleted either for ERα-AF1 (ERα-AF10) and ERα-AF2 (ERα-AF20) nuclear sub-functions or harboring the C451A mutation of the palmitoylation site that abrogates membrane ERα signaling (ERα-C451A), treated or not with E2 (Figure 1A).