Correlation between effects of <i>ATAD2</i> and MYC knockdown.

<p>Western blots for (a) ATAD2 and (b) MYC indicate extent of knockdown with six shRNAs against <i>ATAD2</i> and three shRNAs against MYC, respectively. ATAD2 experiments were performed in KLE cells and MYC experiments were performed in TE9 cells infected with GFP control and MYC vectors. Subsequent experiments used <i>ATAD2</i> shRNAs a and e, and MYC shRNAs a and b. Reductions in cell viability among seven endometrial cancer cell lines (c) and 21 breast cancer cell lines (d) were highly correlated after knockdown of ATAD2 or MYC and after knockdown of MYC and treatment with the HDAC inhibitor Trichostatin-A (1.25 µM) (e–f).</p

Amplification of 8q24, <i>ATAD2</i> overexpression and increased <i>MYC</i> signaling are associated with poor prognosis.

<p>FISH probes against 8q24 (red) and the chromosome 8 centromere (green) in a primary tumor and the paired metastasis show amplification only in the latter (a) (b) Among 399 patients assessed by FISH, those with 8q24 amplifications have worse outcome. In the primary investigation series, tumors among the highest quartiles of (c) <i>ATAD2</i> expression and (d) MYC signaling strength also had increased risk of disease-specific death. (e) Estrogen receptor negative (ER−) tumors with <i>ATAD2</i> expression in the top quartile were also associated with a high risk of disease-specific death; the risk was much lower among estrogen receptor positive (ER+) tumors with <i>ATAD2</i> expression in the bottom quartile. (f) <i>ATAD2</i> expression and (g) MYC signaling are both higher among metastases than primary tumors in the internal validation series.</p

3-D-plots showing <i>ATAD2</i> expression and -copy-number and E2F1 expression.

<p>(a) Endometrial cancer, (b) breast cancer, (c) ovarian cancer, and (d) glioblastoma. Yellow dots represent the samples and the blue plate is the predicted 3-D fit. The green and red lines are the distance between the predicted fit and the actual observations for samples above and below the 3D-fit plate, respectively.</p