[Frontiers in Bioscience 18, 1445-1459, June 1, 2013]

The role of BRCA1 and BRCA2 in prostate cancer

Dan Li1,3, Easwari Kumaraswamy1,3, Lisa M. Harlan-Williams2,3, Roy A. Jensen1,2,3

1Department of Pathology & Laboratory Medicine, 2Department of Anatomy & Cell Biology and 3The University of Kansas Cancer Center, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. BRCA1 and BRCA2 sequence variants and prostate cancer
3.1. BRCA1/2 founder variants in the Ashkenazi Jewish population
3.2. BRCA2 founder variant in the Icelandic population
3.3. BRCA1 founder variants in the Polish population
3.4. BRCA1 founder variant in the Galician population
3.5. BRCA1/2 variants in ethnically mixed population
3.5.1. United Kingdom (U.K.) population
3.5.2. Other populations
3.6. BRCA1 c.1067A>G (Gln356Arg) variant
3.7. IMPACT prospective study
3.8. Summary 4. BRCA1 and BRCA2 in prostate cancer biology
4.1. BRCA1 co-regulators
4.1.1. Direct binding of BRCA1 with androgen receptor (AR)
4.1.2. Direct binding of BRCA1 with Janus kinase (JAK)
4.1.3. Transcriptional complex of BRCA1/E2F-1/Rb and BRCA1/E2F-1/CtIP
4.1.4. BRCA1 regulates insulin-like growth factor 1 receptor (IGF-IR)
4.2. BRCA2 co-regulators
4.2.1. Prostate neoplastic transformation
4.2.2. Prostate cancer progression
4.3. Chemical regulators of BRCA1/2 expression
4.4. Summary
5. Perspective
6. Acknowledgements
7. References

1. ABSTRACT

The familial aggregation of prostate cancer and breast cancer has been observed for almost half a century and about 85% of the inherited breast cancer can be linked to germ-line mutations of BRCA1 (breast cancer 1, early onset) and BRCA2. In this review, we are mainly focusing on the contribution of BRCA1/2 sequence variations to prostate cancer risk and disease progression. We will discuss the biological functions of BRCA1/2 and BRCA1/2-related signaling pathways in prostate cancer biology. The majority of studies supporting the link between BRCA1/2 mutations and prostate cancer are from populations with a high frequency of mutations, such as Ashkenazi Jewish, Icelandic, and U.K. population. BRCA1 can directly interact with the androgen receptor (AR) and Janus kinase (JAK), and can differentially regulate insulin-like growth factor 1 receptor (IGF-IR) expression in an AR-dependent manner. BRCA2 homeostasis in prostate cancer cells has been found to be critical in determining cell fates during prostate cancer progression. This review may be helpful for medical professionals and prostate cancer patients when discussing prostate cancer risks, treatment and prognosis.