Abstract
This study aims to explore the mechanism by which the Translationally controlled tumor protein (TCTP) promotes hyperplasia of the mammary glands (HMG). In this study, the TCTP (Tpt1flox/flox) and TCTP (Tpt1KI/KI) gene mice were respectively mated with MMTV-Cre to obtain mice withmammary glands-specific TCTP knockout (TCTP cKO) and overexpression (TCTP KI). Prepare the HMG animal model by using estrogen combined with progesterone. After the establishment of the TCTP cKO and TCTP KI mouse models, they are uniformly referred to as HMG cKO and HMG KI. Hematoxylin and Eosin (H&E) staining and hormone and receptor expression levels were detected. Detect the levels of TCTP, P53, p-AKT, as well as the indicators related to cell apoptosis and cell cycle in the breast tissues of each group. The H&E results showed that compared with the HMG group, the ductal cavity dilation and the number of milk glands in the breast tissue of the HMG cKO group were significantly reduced, while the HMG KI group exhibited obvious mammary gland hyperplasia. The results showed that compared with the HMG group, the expression levels of Ki67, E2, FSH, LH, ERα, PR, TCTP, p-AKT, p-BAD, Bcl-2, Cyclin D1, CDK4 and CDK6 in the mammary tissues of the HMG cKO group were significantly decreased, while the expression levels of PROG, ERβ, P53, Bax and P27 were significantly increased. In the HMG KI group, the opposite results were observed. In our research, it was confirmed that TCTP inhibits cell apoptosis and promotes cell cycle progression by regulating the AKT/P53 signaling pathway, leading to abnormal hyperplasia of the mammary glands. In HMG, by regulating the expression level of TCTP, the effect of treating HMG can be achieved.
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Data availability
The datasets used and/or analysed during the current study available from the corresponding author (Jun-Fei Zhang E-mail: zhangjunfei007@126.com) on reasonable request.
Abbreviations
- TCTP:
-
Translationally controlled tumor protein
- HMG:
-
Hyperplasia of the mammary glands
- H&E:
-
Directory of open access journals
- E2:
-
Estradiol
- LH:
-
Luteinizing hormone
- FSH:
-
Follicle-stimulating hormone
- PROG:
-
Progesterone
- IHC:
-
Immunohistochemistry
- mIHC:
-
Multiplex Immunofluorescence
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Acknowledgements
We thank Ningxia Keji Biological Co., Ltd., for providing technical support in the histopathological experiments.
Funding
This study was supported by the National Natural Science Foundation of China (82205116; 82160958), the Natural Science Fund of Inner Mongolia (2021MS08077; 2021BS08022).
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ZJF, ML, MMY, LJ, WS and JXM designed the study. SY, CYM, YB and DHH performed multiple experiments and wrote the manuscript.
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All animal procedures were carried out in accordance with the regulations of the Animal Protection Committee of Ningxia Medical University, and all experimental procedures were approved by the Ethics Committee of the General Hospital of Ningxia Medical University (KYLL-2022-0094).
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Ma, MY., Wang, S., Jin, XM. et al. Regulation of the AKT/P53 signaling pathway by translated control tumor protein inhibits apoptosis and promotes hyperplasia of the mammary glands. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43565-x
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DOI: https://doi.org/10.1038/s41598-026-43565-x
