AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating CDKI-cyclin D1 and caspase-3 activity

Dae-Kwan Yoon1, Chul-Ho Jeong, Hyoung Oh Jun

  • 1NeuroVascular Coordination Research Center, Division of Pharmaceutical Biosciences, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.

Cancer Letters
|April 20, 2007
PubMed

Insights

A-Kinase anchoring protein 12 (AKAP12) suppresses tumor cell viability by inducing apoptosis and regulating cell cycle progression. This protein kinase C substrate is down-regulated in various cancers, suggesting its role as a tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • A-Kinase anchoring protein 12 (AKAP12) functions as a protein kinase C substrate and a potential tumor suppressor.
  • AKAP12 is frequently downregulated by oncogenes and suppressed in prostate, ovarian, and breast cancers.
  • AKAP12 regulates mitogenesis by anchoring key signaling proteins like PKA, PKC, and cyclins.

Purpose of the Study:

  • To investigate the role of AKAP12 in suppressing tumor cell viability.
  • To elucidate the molecular mechanisms underlying AKAP12-mediated tumor suppression, focusing on apoptosis and cell cycle regulation.

Main Methods:

  • Transfection of HT1080 cells with AKAP12.
  • Analysis of apoptosis markers, including caspase-3, Bcl-2, and Bax expression.
  • Assessment of cell cycle regulatory proteins, such as Cip1/p21, Kip1/p27, and cyclin D1.

Main Results:

  • AKAP12 transfection suppressed tumor cell viability in HT1080 cells by inducing apoptosis via caspase-3.
  • AKAP12-induced apoptosis correlated with decreased Bcl-2 and increased Bax expression.
  • AKAP12 significantly upregulated Cip1/p21 and Kip1/p27 while decreasing cyclin D1, inhibiting G1 cell cycle progression.

Conclusions:

  • AKAP12 plays a critical role in tumor growth suppression.
  • AKAP12 induces apoptosis and regulates cell cycle progression through modulation of key molecular targets.
  • AKAP12 represents a potential therapeutic target for cancer treatment.

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