JAGGED1 expression is associated with prostate cancer metastasis and recurrence.
Recent studies suggest that NOTCH signaling can promote epithelial-mesenchymal transitions and augment signaling through AKT, an important growth and survival pathway in epithelial cells and prostate cancer in particular. Here we show that JAGGED1, a NOTCH receptor ligand, is significantly more highly expressed in metastatic prostate cancer as compared with localized prostate cancer or benign prostatic tissues, based on immunohistochemical analysis of JAGGED1 expression in human tumor samples from 154 men. Furthermore, high JAGGED1 expression in a subset of clinically localized tumors was significantly associated with recurrence, independent of other clinical parameters. These findings support a model in which dysregulation of JAGGED1 protein levels plays a role in prostate cancer progression and metastasis and suggest that JAGGED1 may be a useful marker in distinguishing indolent and aggressive prostate cancers.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Sandro
S
Santagata
Francesca
F
Demichelis
Alberto
A
Riva
Sooryanarayana
S
Varambally
Matthias D
MD
Hofer
Jeffery L
JL
Kutok
Robert
R
Kim
Jeffery
J
Tang
James E
JE
Montie
Arul M
AM
Chinnaiyan
Mark A
MA
Rubin
Jon C
JC
Aster
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D002135:Calcium-Binding Proteins; D045744:Cell Line, Tumor; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology; D000072099:Serrate-Jagged Proteins
D000906:Antibodies; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins