A 45-year-old woman with breast carcinoma undergoes next-generation sequencing. The tumor shows PIK3CA mutation, PTEN loss, and HER2 amplification. The downstream kinase constitutively activated by loss of PTEN that is critical to HER2-driven proliferation is:
- A AKT/PKB via the PI3K-PIP3 axis ✓
- B RAF-MEK-ERK via the KRAS pathway
- C JAK2-STAT3 via cytokine receptor signaling
- D CDK4/6 via cyclin D1 upregulation
Correct answer: A. AKT/PKB via the PI3K-PIP3 axis
Explanation
PTEN is the phosphatase that converts PIP3 back to PIP2, thereby inhibiting AKT/PKB activation. Loss of PTEN results in constitutive accumulation of PIP3 and persistent AKT activation, which in combination with PIK3CA mutation and HER2 amplification drives proliferation and survival signaling. RAF-MEK-ERK is downstream of KRAS/BRAF, not PTEN. JAK-STAT is activated by cytokine and hormonal receptors independently. CDK4/6 is downstream of multiple pathways but is not the direct product of PTEN loss.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.