NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Commonly down-regulated in human prostate cancer.
NKX3.1 is a homeobox transcription factor that is normally highly expressed in prostate luminal epithelial cells.
– During prostate tumorigenesis, NKX3.1 expression is frequently downregulated or lost, particularly in higher-grade lesions and advanced disease.
Reduced or absent NKX3.1 expression is generally associated with poor prognosis.
Loss of NKX3.1 leads to:
-Increased oxidative DNA damage
-Impaired DNA repair fidelity
-Dedifferentiation of prostate epithelium
-Increased susceptibility to oncogenic transformation (e.g., cooperation with PTEN loss)
NKX3.1 loss does not drive proliferation directly—it removes safeguards that normally restrain malignant evolution.
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