Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells

摘要

A To determine NUPR1 expression levels in breast cancer cell lines as indicated, RT-PCR products were evaluated by agarose gel electrophoresis. RNA levels were normalized to GAPDH expression. bp base pairs. B Immunoblots were carried out with anti-NUPR1 and anti-ACTB antibodies in the cell lines used in A. Experiments in both A and B were performed in triplicate, yielding similar results. Lower panel, NUPR1 relative protein level. C Endogenous NUPR1 was induced by 0.4 µM Tam in ESR1-positive breast cancer cell lines as indicated. Western blot analysis of these cells treated for the indicated time was carried out as described in B. D Representative distribution of NUPR1 by IHC in clinical breast cancer specimens and their adjacent noncancerous tissues from the patient of origin (IHC, brown). Scale bars, 50 μm. E Kaplan–Meier plots of overall survival after surgery for 133 breast cancer subjects with low (0–5.0 staining scores, blue lines; n = 91) or high (5.1–10.0 staining scores, green lines; n = 42) NUPR1 expression (P = 0.0021). The hazard ratio for high NUPR1 expression was 6.998 (CI 4.128–11.862, log-rank test). Median survival was more than 95.4 months for the low NUPR1 expression group versus 68.1 months for the high NUPR1 expression group.