• What is PTEN?
  • PTEN in Lung Cancer
  • Clinical Trials

PTEN

PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a lipid/protein phosphatase that plays a role in multiple cell processes, including growth, proliferation, survival, and maintenance of genomic integrity. PTEN acts as a tumor suppressor by negatively regulating the PI3K/AKT signaling pathway (Figure 1) via dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) at the cell membrane.

Cancer-associated alterations in PTEN often result in PTEN inactivation and thus increased activity of the PI3K-AKT pathway. Somatic mutations of PTEN occur in multiple malignancies, including gliomas, melanoma, prostate, endometrial, breast, ovarian, renal, and lung cancers. Germline mutations of PTEN lead to inherited hamartoma and Cowden syndrome (for reviews see Chalhoub and Baker 2009 and Maehama 2007). PTEN activity can also be lost through other mechanisms such as epigenetic changes or post-translational modifications (Leslie and Foti 2010). Immunochemistry is often used to detect changes in expression of PTEN in tumor tissues; low expression is thought to indicate loss of PTEN expression, which would result in increased activity of the PI3K-AKT pathway.

mapk-pk13.png

Figure 1.
Schematic of the MAPK and PI3K pathways. Growth factor binding to receptor tyrosine kinase results in activation of the MAPK signaling pathway (RAS-RAF-MEK-ERK) and the PI3K pathway (PI3K-AKT-mTOR). The letter "K" within the schema denotes the tyrosine kinase domain.

Related Pathways

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. PTEN. My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/pten/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

PTEN in Non-Small Cell Lung Cancer (NSCLC)

Somatic mutations in PTEN have been found in 4–8% of all NSCLC (Jin et al. 2010; Kohno et al. 1998; Lee et al. 2010). PTEN mutations are found more commonly in ever smokers and in tumors with squamous cell histology (Jin et al. 2010; Lee et al. 2010). PTEN mutation can occur in multiple exons within the gene (i.e., no 'hotspot' mutations in PTEN have been found; Jin et al. 2010).

Contributors: Christine M. Lovly, M.D., Ph.D., Leora Horn, M.D., M.Sc., William Pao, M.D., Ph.D. (through April 2014)

Suggested Citation: Lovly, C., L. Horn, W. Pao. 2015. PTEN in Non-Small Cell Lung Cancer (NSCLC). My Cancer Genome https://www.padiracinnovation.org/content/disease/lung-cancer/pten/ (Updated June 18).

Last Updated: June 18, 2015

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