PTEN (phosphatase and tensin homolog deleted on chromosome 10) is the protein which is encoded by the PTEN gene. The PTEN protein is found in almost all tissues in the body. PTEN is involved in the regulation of the cell cycle by preventing cells from growing and dividing too rapidly. The PTEN gene was identified as a tumor suppressor gene that is mutated in a large number of cancers at high frequency. These include cancers of the breast, prostate, endometrium, ovary, brain, skin, thyroid, lung, bladder and colon, as well as melanoma, glioblastoma. and lymphoma (Teng et al., Cancer Res. 57: 5221-5225, 1997) During tumor development, mutations and deletions of PTEN occur that inactivate its enzymatic activity leading to increased cell proliferation and reduced cell death. Genetic inactivation of PTEN occurs in glioblastoma, endometrial cancer, prostate cancer, and reduced expression is found in many other tumor types, such as lung and breast cancer.
PTEN mutations also cause a variety of inherited predispositions to cancer. For example, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome and Proteus-like syndrome. Together, the disorders caused by PTEN mutations are called PTEN hamartoma tumor syndromes, or PHTS. Mutations responsible for these syndromes cause the resulting protein to be nonfunctional or absent. The defective protein allows the cell to divide in an uncontrolled way and prevents damaged cells from dying, which can lead to the growth of tumors.
The prevalence of PTEN mutations in cancer underscores the significance of finding methods and compositions to treat, diagnose, and prevent such diseases. However, perhaps because of the many cellular biochemical reactions in which PTEN phosphatase activity is implicated in, or because of the nature of tumor suppressor genes, treatments that directly target PTEN activity or expression have had limited success. Thus, a need exists to develop new methods and compositions to identify patients suitable for treatment, treatments, diagnosis and prognosis of cancer and related diseases in which PTEN is mutated or lost.