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Background <p>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 NKX3.1<sup>em1Hlee</sup>/Korl KO (NKX3.1 KO) mice injected with TS for six weeks.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Exogenous testosterone exacerbates pre-neoplastic lesions in the prostate of NKX3.1-deficient mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月26日

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  • Su Jeong Lim,
  • Jin Ju Park,
  • Ji Eun Kim,
  • Hee Jin Song,
  • Ayun Seol,
  • Su Ha Wang,
  • Ye Eun Ryu,
  • Ye Ryeong Kim,
  • Jun Go,
  • Dae Youn Hwang

摘要

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.