Functional analysis of the host defense peptide Human Beta Defensin-1: new insight into its potential role in cancer.
Although it is known that innate immunity is key for protecting the body against foreign agents such as bacteria, little is known about elements of the innate immune system that have anti-tumor activity. Human Beta Defensin-1 (hBD-1), an important component of the innate immune response, is lost at high frequencies in malignant prostatic tissue, while high levels of expression are maintained in adjacent benign regions. In prostate carcinoma, frequent genetic alterations occur in the 8p22-23 region and several studies indicate there may be multiple tumor suppressor genes present within this region. The high incidence of loss of hBD-1 expression in prostate cancer, along with its chromosomal location of 8p23.2, raised the possibility that it may play a role in tumor suppression. To gain insight as to its function in prostate cancer, hBD-1 was cloned and ectopically expressed in four prostate cancer cell lines. Induction of hBD-1 expression resulted in a decrease in cellular growth in DU145 and PC3 cells. However, hBD-1 has no effect on the growth of androgen receptor (AR) positive LNCaP prostate cancer cells, but was again growth suppressive to PC3 cells with ectopic AR expression (PC3/AR+). hBD-1 also caused rapid induction of cytolysis and caspase-mediated apoptosis in DU145 and PC3 prostate cancer cells. Although the regulation of hBD-1 was not addressed in this study, our preliminary data demonstrated that the pathways involved may include cMYC and PAX2. Data presented here are the first to provide evidence of its potential role in prostate cancer cell death.
Bullard
Rebecca S
RS
Department of Pathology and Laboratory Medicine, 165 Ashley Avenue, PO Box 250620, Charleston, SC 29425, USA.
Gibson
Willietta
W
Bose
Sudeep K
SK
Belgrave
Jamila K
JK
Eaddy
Andre C
AC
Wright
Corey J
CJ
Hazen-Martin
Debra J
DJ
Lage
Janice M
JM
Keane
Thomas E
TE
Ganz
Tomas A
TA
Donald
Carlton D
CD
D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics / Q000276:immunology; D003001:Cloning, Molecular; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*
C406407:DEFB1 protein, human; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins; D023083:beta-Defensins