Navigate Up

Beth R. Pflug, PhD

Growth Regulation and Prostate Cancer
Our laboratory is interested in gaining a better understanding of the growth regulation of prostate cancer and using this information to identify novel therapeutic and imaging targets for this disease. One aspect of our research focuses on new treatment strategies, such as endothelin receptor blockade, to combat advanced prostate disease. To date, hormone ablation is the most common treatment for advanced disease. Ablation initially decreases tumor size, but it does not result in a permanent remission and so the majority of patients eventually present with recurrent hormone-refractory tumors. Endothelin-1 (ET-1) has been identified as an important growth factor in the pathophysiology of androgen-refractory prostate cancer. These findings have been applied to the clinic, and trials using endothelin receptor blockade have demonstrated significant clinical benefit in patients with advanced prostate cancer. We have shown that both ET-1 and one of its receptors, ETA, undergo up-regulation after androgen ablation. Moreover, activation of the ETA signaling pathway results in inhibition of apoptosis. These observations have led to our hypothesis that the ET axis provides a survival mechanism for prostate cancer cells facing androgen ablation; a key event in the evolution of androgen-refractory disease. Continuation of our work involving the endothelin axis includes further characterizing ET-1 signaling pathways in prostate cancer and expanding the therapeutic targets for prostate cancer treatment. These studies will also help identify those patients most likely to respond to endothelin receptor blockade through analysis of the ET axis. Other research interests include the co-modulation of bone and prostate cancer cell growth. Metastatic prostate cancer commonly resides in the bone during the progression of androgen refractory disease. Our laboratory is examining bone cell/prostate cancer cell interactions to further identify new mechanisms for therapeutic intervention for prostate cancer patients with metastatic disease to the bone.

Fatty Acid Synthase and Prostate Cancer
In addition to the studies on the endothelin axis, our laboratory is also pursuing studies in altered cell metabolism during prostate cancer progression. Fatty acid synthase (FAS) is the major multifunctional enzyme required by cells to convert carbohydrates to fatty acids de novo. FAS protein levels and enzyme activity are low in most normal tissues, but become up-regulated in prostate cancer. Our studies investigate the role of FAS and lipids during androgen-dependent and -independent prostate tumorigenesis using in vitro and transgenic mouse models, and examine the effects of FAS anti-metabolite therapy on cell death and tumor regression. Overexpression of FAS in prostate cancer cells also makes this molecule a potential imaging target for positron emission tomography (PET). Thus, our laboratory is exploring the use of PET imaging for the study of FAS in local and metastatic prostate tumors, with the ultimate goal of developing this technique into a method for imaging advanced disease.

For more information regarding graduate work in my lab, please go to the University of Pittsburgh Graduate faculty website (http://path.upmc.edu/cmp/fac43.htm)

Selected Publications

    1. Akhavan A, McHugh KH, Guruli G, Bies RR, Zamboni WC, Strychor SA, Nelson JB and Pflug BR. (2006) Endothelin receptor A blockade enhances taxane effects in prostate cancer. Neoplasia 8:725-732.
    2. Pflug BR, Zheng H, Udan MS, Marshall FF, Brooks JD and Nelson JB. (2006) Endothelin-1 promotes cell survival in renal cell carcinoma through the ETA receptor. Cancer Letters 246:139-148.
    3. Shah US, Dhir R, Gollin S, Lewis D, Chandran UR, Acquafondata M and Pflug BR. (2006) Fatty acid synthase gene expression amplification in prostate adenocarcinoma. Human Pathology 4: 401-409.
    4. Nelson JB, Udan MS, Guruli G and Pflug BR. (2005) Endothelin-1 inhibits apoptosis in prostate cancer. Neoplasia 7:631-637.
    5. Godara G, Cannon G, Cannon G, Jr., Nelson JB and Pflug BR. (2005) Role of endothelin axis in progression to aggressive phenotype of prostate adenocarcinoma. The Prostate 65:27-34.
Beth R. Pflug, PhD

Contact Information

Office phone: 412-623-3915
Lab phone: 412-623-3932
 

Additional Resources

©  UPMC | Affiliated with the University of Pittsburgh Schools of the Health Sciences
Supplemental content provided by A.D.A.M. Health Solutions. All rights reserved.

For help in finding a doctor or health service that suits your needs, call the UPMC Referral Service at 412-647-UPMC (8762) or 1-800-533-UPMC (8762). Select option 1.

UPMC is an equal opportunity employer. UPMC policy prohibits discrimination or harassment on the basis of race, color, religion, ancestry, national origin, age, sex, genetics, sexual orientation, marital status, familial status, disability, veteran status, or any other legally protected group status. Further, UPMC will continue to support and promote equal employment opportunity, human dignity, and racial, ethnic, and cultural diversity. This policy applies to admissions, employment, and access to and treatment in UPMC programs and activities. This commitment is made by UPMC in accordance with federal, state, and/or local laws and regulations.

Medical information made available on UPMC.com is not intended to be used as a substitute for professional medical advice, diagnosis, or treatment. You should not rely entirely on this information for your health care needs. Ask your own doctor or health care provider any specific medical questions that you have. Further, UPMC.com is not a tool to be used in the case of an emergency. If an emergency arises, you should seek appropriate emergency medical services.

For UPMC Mercy Patients: As a Catholic hospital, UPMC Mercy abides by the Ethical and Religious Directives for Catholic Health Care Services, as determined by the United States Conference of Catholic Bishops. As such, UPMC Mercy neither endorses nor provides medical practices and/or procedures that contradict the moral teachings of the Roman Catholic Church.

© UPMC
Pittsburgh, PA, USA UPMC.com