Transforming Growth Factor-Beta in Prostate Cancer

Part of the Protein Reviews book series (PRON, volume 16)


TGF-βs are 25 kDa dimeric proteins that function through autocrine, paracrine, and endocrine mechanisms to regulate a diverse array of cellular and physiological processes in numerous tissues. Deregulation of TGF-β signaling is involved in the pathophysiology of prostate cancer. Central to normal prostate epithelial and stromal cell growth control mechanisms, TGF-β functions as a tumor suppressor and an important regulator of androgenic responses. Particularly striking, androgen withdrawal activates multiple components of the TGF-β signaling pathway in the normal prostate, which then partake in the ensuing apoptotic cell death response. Multiple discreet alterations in TGF-β signaling responses occur during the process of carcinogenesis and tumor progression, which contribute to the development of both metastatic disease and ultimately to castrate-resistant prostate cancer (CRPC). Despite its seemingly straightforward role as a tumor suppressor in the normal prostate, there is accumulating evidence supporting that the function of TGF-β “switches” to a tumor promoter during carcinogenesis/tumor progression. This represents what has now been coined the “TGF-β paradox,” the molecular and physiological basis for which remains incompletely defined. The TGF-β paradox also imposes inevitable complexities in therapeutic strategies involving TGF-β. However, recent advances provide significant promise for TGF-β as a prognostic marker and therapeutic target of prostate cancer (PCa).

This chapter provides a current overview of key components of the TGF-β signaling pathway. Starting with some historical perspective, the chapter highlights fundamentals of the TGF-β ligand structure, regulation of expression, storage, and activation. Next illustrated are the nuts and bolts of TGF-β receptor and Smad ­structure and function. A thorough perspective and mechanistic insight is provided on the current understanding in the field of TGF-β in normal and malignant prostate and state-of-the-art progress on TGF-β-based preclinical and clinical therapeutic opportunities.


Androgen Receptor LNCaP Cell Prostate Intraepithelial Neoplasia Normal Prostate Epithelium Endogenous Androgen Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The author is in debt for Dr. Donald Tindall’s excellent editorial help. This work was supported in part by NIH grants R01 CA134878 and P30 CA43703.


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Copyright information

© Mayo Clinic 2013

Authors and Affiliations

  1. 1.Division of General Medical Sciences, Department of Pharmacology, Case Comprehensive Cancer CenterCase Western University School of MedicineClevelandUSA
  2. 2.Department of UrologyUniversity Hospitals of ClevelandClevelandUSA

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