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. 2021 Apr 23;11:8847. doi: 10.1038/s41598-021-87492-5

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Pathological findings in aged female transgenic mice. A: IHC staining with anti-CK-8 antibody on masses derived from TG-LH-R-frt-105, TG-LH-R-frt-200 and TG-LH-R-frt-123. Nuclei are counterstained with hematoxylin. Bar = 200 μm a: histogram summarizing CK-8 scoring in the different tumor masses (TG-LH-R-frt-105 mass: 86 ± 4.5; TG-LH-R-frt-200 mass: 172 ± 4.4 and TG-LH-R-frt-123 mass: 155 ± 3; WT score = 0). B: Representative IHC pictures of masses derived from TG-LH-R-frt-105, TG-LH-R-frt-200 and TG-LH-R-frt-123 labelled with anti-c-myc antibody. Nuclei are counterstained with hematoxylin. b: Histogram summarizing c-myc scoring in the different tumor masses (TG-LH-R-frt-105, TG-LH-R-frt-200: 75 ± 3, TG-LH-R-frt-123: 105:160 ± 6). C: histograms summarizing pAKT. ERK, VEGF, Ki67 and p53 scoring in the different tumors (pAKT: WT: 12 ± 5; healthy TG-LH-R-frt-100 40 ± 7; healthy TG-LH-R-frt-200 55 ± 5; TG-LH-R-frt-123 mass: 160 ± 17.3; TG-LH-R-frt-200 mass: 186 ± 6.6; TG-LH-R-frt-105 mass: 180 ± 11.5. ERK: WT: 13 ± 2; healthy TG-LH-R-frt-100: 55 ± 13; healthy TG-LH-R-frt-200: 46 ± 12; TG-LH-R-frt-123 mass: 190 ± 5; TG-LH-R-frt-200 mass: 173 ± 3.5; TG-LH-R-frt-105 mass: 290 ± 5. VEGF: WT: 11 ± 1, healthy TG-LH-R-frt-100: 77 ± 9, healthy TG-LH-R-frt-200: 57 ± 8.8, TG-LH-R-frt-123 mass: 173 ± 7, TG-LH-R-frt-200 mass: 163 ± 3; TG-LH-R-frt-105 mass: 275 ± 5. Ki67: WT: 8 ± 1.5, healthy TG-LH-R-frt-100: 13 ± 3.7, healthy TG-LH-R-frt-200: 11 ± 3.8, TG-LH-R-frt-123 mass: 96.6 ± 9, TG-LH-R-frt-200 mass: 96.6 ± 9; TG-LH-R-frt-105 mass: 133 ± 24. P53: WT: 13 ± 4, healthy TG-LH-R-frt-100: 35 ± 10, healthy TG-LH-R-frt-200: 33 ± 11, TG-LH-R-frt-123 mass: 115 ± 7.5, TG-LH-R-frt-200 mass: 108 ± 7.5; TG-LH-R-frt-105 mass: 150 ± 17.3). D: Representative IHC picture using image anti-hERG1 antibody on the uterus of WT mouse and the mass derived from TG-LH-R-frt-200. The expression of hERG1 and c-myc is evaluated in adjacent tumor sections. Nuclei are counterstained with hematoxylin. Bar = 200 μm. d: Histogram summarizing hERG1 score quantification in the different samples (WT: 0, healthy TG-LH-R-frt-100 mice: 0, healthy TG-LH-R-frt-200 mice: 0, TG-LH-R-frt-123 mass: 226 ± 7, TG-LH-R-frt-105 mass: 141 ± 11 and TG-LH-R-frt-200 mass: 126 ± 5). E: Scatter plot of hERG1, pAKT, ERK and VEGF in the three different masses. Values are means ±SEM. c-myc vs hERG1: p = 0.014, R=0.8991; c-myc vs pAKT: p = 0.013, R = 0.9048; c-myc vs ERK: p = 0.0017, R = 0.9661; c-myc vs VEGF: p = 0.005, R = 0.9431; c-myc vs Ki67: p = 0.007, R = 0.9275; c-myc vs p53: p = 0.002, R = 0.9624 (p-values are evaluated by Student’s t test; R = Pearson Correlation Coefficient).