[Frontiers in Bioscience 7, e245-251, May 1, 2002]

BIOLOGICAL ROLE OF PHOSPHATASE PTEN IN CANCER AND TISSUE INJURY HEALING

Kouji Tsugawa 1,2, Michael K. Jones 1, Keizo Sugimachi 2, I. James Sarfeh 1, and Andrzej S. Tarnawski 1

1 Departments of Medicine and Surgery, Department of Veterans Affairs Medical Center, Long Beach, California, University of California, Irvine, California, and 2 Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan

TABLE OF CONTENT

1. Abstract
2. What is PTEN?
3. Biological Role and Functions of PTEN
4. Where is PTEN encoded and where is it localized?
5. Reactions catalyzed by PI 3-kinase and PTEN
6. Cell survival and proliferation are enhanced by PI 3-kinase and Akt, and are suppressed by PTEN
7. Overexpression or enhanced activation of PTEN can potentially impair tissue injury healing by at least 4 mechanisms
8. PTEN abrogation is implicated in cancer progression
9. Regulation of PTEN activity
10. Conclusions
11. Acknowledgement
12. References

1. ABSTRACT

PTEN (phosphatase and tensin homolog deleted on chromosome ten) also referred to as MMAC (mutated in multiple advanced cancers) was discovered as a tumor suppressor gene and later found to be a phospholipid phosphatase. PTEN negatively regulates Akt activation by preventing its phosphorylation. PTEN therefore inhibits the PI 3-kinase/Akt signaling pathway which is important for cell growth and survival. Overexpression or enhanced activation of PTEN can potentially impair injury healing by at least 4 mechanisms. PTEN can: 1) inhibit entry into the cell cycle by inhibiting G1 to S phase progression and arrest cell proliferation required for tissue reconstruction during injury healing; 2) increase apoptosis by blocking Akt activation leading to increased Bad and Caspase-9 activities; 3) inhibit hypoxia-induced angiogenesis required for injury healing by blocking Akt-mediated VEGF gene transcription; 4) inhibit Akt-mediated cell migration, i.e. re-epithelialization, which is also required for injury healing. The same mechanisms can also suppress cancer growth and metastases. Therefore, elucidating the role of the PTEN/PI 3-kinase/Akt pathway will likely advance our knowledge of the mechanisms controlling the processes of injury healing and cancer growth.