BASIC SCIENCE RESEARCH PROGRAM
Research projects are integrated under the following themes which are highly interactive and are beyond the conventional boundaries of a given expertise area and truly represent the CPDR paradigm:
- Translational CaP Genomics and Proteomics
- Novel CaP Cell Culture Models
- CaP Molecular Genetics
- Hormonal Mechanisms of CaP
Translational CaP Genomics and Proteomics
Translational research of cancer cell and molecular biology-derived discoveries in the pre-clinical or clinical research setting has been the priority of CPDR since its inception. A highly multi-disciplinary research environment of urologists, cancer cell and molecular biologists, genitourinary pathologists, bioinformatics and medical informatics experts, bio-statisticians, medical technologists and regulatory affairs experts supports the CPDR enterprise. Well-characterized CPDR biospecimens banks, recent discoveries showing consistent gene expression alterations in CaP and development of promising new molecular diagnostic technologies, have provided an optimal setting for CPDR to focus in the translational research areas, where we already have developed expertise or in the areas where new initiatives are needed.
Novel Cell Culture Models of CaP
The Prostate Cell Center was established in the newly-renovated CPDR laboratory at the Department of Surgery, USUHS, in January 2000 and has been very active over the years. The Prostate Cell Center has made major advances in the generation of short-term cultures from primary tumors of prostate cancer patients. (1) Total cell strains generated from primary tumors are 134, (2) the number of cell strains generated from normal tissue from the same patient are 72, (3) five well-characterized telomerase-immortalized human CaP cell lines from the tumor of African American and caucasian CaP patients. These cells are critical to the development and use of in vitro models and for the identification of novel therapeutic targets of prostate cancer.
CaP Molecular Genetics
Since its inception, CPDR-BRP has embraced the goal of defining CaP-specific genetic alterations that characterize the disease onset and/or progression. Genetic alterations that are "critical" in the genesis of CaP or molecular alterations that "consistently associate" with CaP will provide definitive molecular targets for the development of bio-markers and new therapeutic targets. This goal has become increasingly more apparent as most of the frequent gene alterations associated with other common human cancers such as breast cancer, colon cancer or lung cancer, do not seem to play a significant role in CaP.
Defining Androgen Signaling in CaP Onset and Progression
Androgen signaling is extremely important in the life and death of the prostate gland and is believed to play an important role in prostate cancer. Hormonal therapy, the most common treatment strategy for the treatment of metastatic prostate cancer works by inhibiting androgen signaling. Accumulating evidence suggests that alterations of androgen signaling in prostate cancer may involve structural or functional alterations of the critical genes at numerous points in the pathway.
Read the FEBRUARY 2014 Newsletter
Loss of the NKX3.1 tumorsuppressor promotes the TMPRSS2-ERG fusion gene expression in prostate cancer
Thangapazham R, Saenz F, Katta S, Mohamed AA, Tan S-H, Petrovics G, Srivastava S and Dobi A.
BMC Cancer. 2014: Jan 13;14:16.
ERG rearrangement and protein expression in the progression to castration-resistant prostate cancer.
Gsponer JR, Braun M, Scheble VJ, Zellweger T, Rentsch CA, Bachmann A, Perner S, Sesterhenn IA,
Srivastava S, Dobi A, Bubendorf L, Ruiz C.
Prostate Cancer Prostatic Dis. 2014 Jan 28. doi: 10.1038/pcan.2013.62. [Epub ahead of print]