PTEN-deleted Human Cell Lines for Detection of Anticancer Compounds
Section: For Industry
Category(ies): Cancer Diagnostics | Cell Lines
Reference #: WATO432803
OTC Contact: Tracy L. Bruehs, M.S., J.D. (Directory Information | Send a Message)
Description
Georgetown University is seeking a licensee for PTEN Deleted Human Cell Lines for Detection of Anticancer Compounds, a cell line which has been deleted for both copies of the PTEN tumor suppressor gene. This invention provides isogenic cell lines for the detection of small molecules which differentially affect cells in which PTEN is inactivated.
Applications
- System for detection of small molecules active against cells in which PTEN tumor suppressor gene is inactive. Human PTEN targeting vectors have been created that make it possible to specifically delete alleles of PTEN in human cells grown in culture. PTEN is inactivated by mutation in a variety of human cancers, including gliobastoma multiforme, endometrial carcinoma, malignant melanoma advanced prostate cancers and others.
- Isogenic cell lines allow detection of compounds which are only active in PTEN deficient cells.
- Requires no detailed knowledge of the biochemical differences between PTEN active and inactive cells
Advantages
Stage of Development
PTEN is a recently identified gene that codes for a dual-specificity phosphatase that dephosphorylates both lipid and protein substrates. It is located in a part of chromosome 10 that is frequently lost in invasive breast cancer. The PTEN gene functions as a 'tumor suppressor', by serving as a 'brake' on certain key cellular growth and signaling pathways. PTEN regulates a number of genes and processes, which collectively we refer to as the PTEN/Akt pathway. As a result, if PTEN becomes lost or altered as a result of chromosome 10 changes, then these cells become permissive for a variety of cancers. HCT116 is a human colon cancer cell line that contains only two copies of each chromosome, unlike the aneuploid state found in many other cell lines. Human PTEN targeting vectors have been created that make it possible to specifically delete alleles of PTEN in these human cells grown in culture. PTEN targeting vectors were employed to create cell lines in which both copies of the PTEN gene have been deleted. These genetically engineered cells can be used in cell-based screens to identify drug candidates that specifically kill cells with mutated PTEN. This is known as "isogenic" cell-based screen. As the only known change in the cell lines is the loss of PTEN, libraries may screened for that differentially affect the isogenic cell lines. The power of the screen is that knowledge of the underlying biochemical pathways altered by loss of PTEN is not required in order to isolate compounds which specifically target PTEN deficient cells.Loss of PTEN functionality is also been correlated with inability of cells to enter into apoptosis. Thus PTEN loss appears to be intimately associated with a variety of cancers.
Relevant Publications
No references or resources available.
Patent Status
US and foreign rights protected
