ERα+ and ERα- carcinomas demonstrate distinct transcript profiles, and are insensitive to ovarian steroids. (a) Hierarchical clustering of genes and tumor samples demonstrates differential expression between ERα+ (yellow) and ERα- (blue) adenocarcinomas at the P < 0.01 significance level (N = 4 each). ERα+ was defined as ≥10% of the cells contained detectable ERα by IHC; ERα- contained <10%. Red indicates high relative expression in ERα positive adenocarcinomas; green, low relative expression; black, no difference. Each column represents an independent tumor, and each row is a gene. (b) Growth of PRL-induced tumors is not diminished by ovariectomy, regardless of ERα status. Mammary carcinomas of distributed histotypes in NRL-PRL nonparous females were biopsied, and the mice subjected to sham surgery or ovariectomy. Subsequent tumor growth was monitored until tumors reached 1.5 cm in diameter (15.3 ± 8.5 days; mean ± s.d.), and proliferation determined by PCNA IHC as described in the Materials and Methods. Sham, N = 12; ovx ERα+, N = 10; ovx ERα-, N = 9. Treatment did not alter the rate of growth (Student's paired t-test, P > 0.05). (c) Treatment with the ER inhibitor and downregulator, Faslodex (ICI 182,780), does not inhibit growth of ERα positive tumor fragments. Fragments of well-differentiated ERα+ tumors were transplanted into fat pads of nontransgenic recipients and treated with ovariectomy, sham surgery, or Faslodex as described in Materials and Methods. Ovariectomized and Faslodex-treated females had significantly reduced uterine weights (27 ± 5 mg, 30 ± 8 mg, mean ± s.d., respectively), compared to sham-treated females (83 ± 5 mg). Treatment did not alter the rate of proliferation (P > 0.05).