Genes that are consistently over-expressed in the vast majority of prostate cancers are of particular interest biologically and clinically. In addition to providing insight into the etiology of prostate cancer, those genes and their products are potentially useful as diagnostic markers, although few such genes have yet been identified.

INNOVATION:  Research at UCLA has resulted in the identification and characterization of a particular transcription factor that offers promise as a new marker for prostate cancer. Yin Yang 1 (YY1) (also known as NF-E1, CP-1 and UCRBP) is a multifunctional DNA binding protein that can activate or repress transcription, depending on the context in which it binds. As previously demonstrated, YY1, which plays an important role in the regulation of many cellular and viral genes, is over-expressed in the human prostate cancer cell line PC3. Its expression has also been shown to be associated with resistance to Fas apoptosis.

Using tissue microarrays to investigate YY1 expression and cellular location in a large sample of patients who had undergone radical prostatectomy, researchers have now determined that YY1 represents a gene product of both prognostic significance in the treatment of prostate cancer and diagnostic potential as a reliable biomarker. The consistency and robust nature of the YY1 transcription factor render it well suited as a diagnostic marker for use in the evaluation of prostate needle biopsy samples.

To date the UCLA researchers have: (a) optimized the use of the YY1 antibody for immunohistochemistry; (b) analyzed tissue biopsies of hundreds of patients following radical prostatectomy; (c) performed statistical analyses of cytoplasm and nuclear staining; (d) established a correlation with several clinical and pathological variables; (e) determined a prognostic significance for patients with weaker nuclear YY1 expression, correlating with more rapid tumor recurrence; and (f) designed YY1 sequence-specific oligonucleotides for semi-quantitative RT-PCR.

ADVANTAGES 

• The potential value of this technology lies in its superior diagnostic and prognostic capabilities and in its promising potential with regard to the development of improved therapeutic for prostate cancer (and potentially for other forms of cancer as well).

POTENTIAL APPLICATIONS 

• Immunohistochemistry analysis of YY1 expression in cell nuclei or cytosol, either independently or in combination with other known markers, following needle biopsy. For example, analysis of YY1 expression in conjunction with tests for the presence of the prostate basal cell marker p63 potentially will enhance diagnostic performance by providing a positive YY1 stain result in addition to a negative p63 stain indicative of cancerous cells.
• Detection of YY1 expression in isolated cells using RT-PCR, following microlaser microdissection.
• Determination of YY1 levels in fresh tumor biopsy tissue by analyzing cell lysates using either ELISA or the Western blot analysis, or by evaluating YY1 DNA-binding activity using EMSA.
• Determination of critical needle biopsy sites and assessment of cancer progression within the prostate, based upon molecular imaging identification of individual cells or cell groups exhibiting YY1 expression characteristic of prostate cancer.
• Detection of metastatic prostate cancer in organs other than the liver and kidney, based upon systematic molecular imaging of YY1 expression.
• Development of predictive methods or tools supportive of prostate cancer patient treatment decisions.
• Development of new therapeutic methods based, for example, upon interference with YY1 expression or activity. Such new methods could prove particularly beneficial in the treatment of prostate cancer determined to be resistant to chemotherapy or immunotherapy.

INVENTOR:  Dr. Benjamin Bonavida is a Professor in the Department of Microbiology, Immunology and Molecular Genetics at UCLA's David Geffen School of Medicine, and is a Member of the Tumor Immunology Research Group at UCLA's Jonsson Comprehensive Cancer Center.

Reference: UCLA Case No. 2004-194

PCT Application: PCT/US05/032391