PTEN

🔍 What is PTEN?

PTEN stands for Phosphatase and TENsin homolog. It encodes a lipid phosphatase that:

• Converts PIP3 back into PIP2
• Effectively inhibits the PI3K/AKT/mTOR signaling pathway, which promotes cell growth and survival.

🛡️ In simple terms: PI3K activates cell growth; PTEN puts on the brakes.

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⚠️ PTEN as a Tumor Suppressor

• In normal cells, PTEN keeps growth signals under control.
• Loss of PTEN function leads to unchecked AKT signaling, driving:
  • Excessive cell proliferation
  • Reduced apoptosis
  • Increased survival of damaged or abnormal cells
  • Genomic instability

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📊 Prevalence of PTEN Loss or Mutation in Cancer

Cancer Type	PTEN Alterations
Endometrial carcinoma	~40–60% (very common)
Glioblastoma	~30–40%
Prostate cancer	~20–50% (especially advanced)
Triple-negative breast cancer	~10–20%
Melanoma	~5–15%
NSCLC	~5–10%
Hematologic malignancies	Rare (<5%)

🔬 Common Alteration Types:

• Point mutations
• Gene deletions
• Promoter methylation (silencing)
• Post-translational inactivation

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⚙️ How PTEN Loss Causes Cancer

1. PIP3 Accumulation
   • PTEN normally converts PIP3 → PIP2
   • Without PTEN, PIP3 accumulates → AKT stays permanently active
2. AKT & mTOR Activation
   • Drives:
     • Protein synthesis
     • Cell cycle progression
     • Inhibition of apoptosis
     • Angiogenesis
3. Genomic Instability
   • PTEN also regulates:
     • DNA repair
     • Chromosomal integrity
   • Its loss increases mutation rates and chromosomal abnormalities

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💊 Clinical Implications