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Updated: Jun 28, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Exogenous testosterone exacerbates pre-neoplastic lesions in the prostate of NKX3.1-deficient mice
Su Jeong Lim1, Jin Ju Park1, Ji Eun Kim1
1Department of Biomaterials Science (BK21 FOUR Program)/Life and Industry Convergence Research Institute/Laboratory Animal Resources Center, College of Natural Resources & Life Science, Pusan National University, Miryang, 50463, Republic of Korea.
Background:
NKX3.1 is a prostate-specific tumor suppressor that is frequently downregulated during the early stages of prostate cancer. Although NKX3.1 knockout (KO) mice develop spontaneous epithelial abnormalities, these lesions rarely progress beyond early neoplastic changes without additional oncogenic stimulus. Therefore, we investigated whether exogenous testosterone (TS) exacerbates early-stage, pre-neoplastic lesions in the prostate of NKX3.1 KO mice. Alterations in prostate weights of male reproductive organs (testis, seminal vesicles, and prostate lobes), histopathological lesion scores, apoptotic proteins, and angiogenic proteins were analyzed in C57BL/6 NKX3.1em1Hlee/Korl KO (NKX3.1 KO) mice injected with TS for six weeks.
Results:
The weight of testis, seminal vesicles and ventral prostate was commonly changed in TS-treated mice of wild type (WT) and NKX3.1 KO group, while those of the dorsolateral and anterior prostate were only increased in TS-treated NKX3.1 KO group compared to those of WT. Histopathological lesion severity was greater in TS-treated NKX3.1 KO mice, with the highest lesion scores observed in the high-dose TS (HiTS)-treated KO group, and a similar pattern was observed for p53 staining. The expression levels of apoptotic and angiogenic proteins were significantly increased in TS-treated NKX3.1 KO mice compared to the same group of WT mice.
Conclusions:
These findings suggest that the exogenous TS exacerbates early-stage, pre-neoplastic lesions in the prostate of NKX3.1 KO mice, consistent with a gene-hormone synergistic interaction. The mechanistic basis of this synergy remains to be defined.
Insights
Testosterone exacerbates early prostate cancer lesions in NKX3.1 knockout mice, indicating a gene-hormone interaction. Further research is needed to define the exact mechanisms driving this synergy.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- NKX3.1 is a prostate tumor suppressor frequently lost in early prostate cancer.
- NKX3.1 knockout mice exhibit pre-neoplastic prostate lesions but rarely progress without additional stimuli.
- The role of exogenous testosterone in exacerbating these early lesions is not well understood.
Purpose of the Study:
- To investigate if exogenous testosterone (TS) worsens early-stage, pre-neoplastic prostate lesions in NKX3.1 knockout (KO) mice.
- To analyze the impact of TS on prostate weight, histopathology, and protein expression in NKX3.1 KO mice.
- To explore potential gene-hormone synergistic interactions in prostate cancer development.
Main Methods:
- NKX3.1 KO mice and wild-type (WT) littermates were injected with TS for six weeks.
- Prostate weights, testis, and seminal vesicles were measured.
- Histopathological lesion scores, p53 staining, apoptotic, and angiogenic protein levels were analyzed.
Main Results:
- Testosterone treatment altered reproductive organ weights, notably increasing dorsolateral and anterior prostate weight in NKX3.1 KO mice.
- Histopathological lesion severity and p53 staining were significantly higher in TS-treated NKX3.1 KO mice.
- Apoptotic and angiogenic protein expression increased in TS-treated NKX3.1 KO mice compared to WT.
Conclusions:
- Exogenous testosterone exacerbates early-stage prostate lesions in NKX3.1 KO mice.
- Findings suggest a synergistic interaction between NKX3.1 gene status and testosterone.
- The precise molecular mechanisms underlying this gene-hormone synergy require further investigation.
