CXCL12 activates a robust transcriptional response in human prostate epithelial cells.
CXCL12 is a CXC-type chemokine that plays important roles in hematopoiesis, development, and organization of the immune system and supports the survival or growth of a variety of normal or malignant cell types. Our laboratory recently showed that CXCL12 is secreted by aging stromal fibroblast cells and is a major paracrine factor that specifically stimulates the proliferation of prostate epithelial cells. The current study shows that this CXCL12-mediated proliferative response may be either ERK-dependent or ERK-independent. Moreover, CXCL12 initiates a previously undefined and complex global transcriptional response in prostate epithelial cells. This CXCL12-mediated transcriptional response directly stimulates the expression of genes encoding proteins that are involved in the promotion of cellular proliferation and progression through the cell cycle, tumor metastasis, and cellular motility, and directly represses the transcription of genes encoding proteins involved in cell-cell adhesion and resistance to apoptosis. Thus, CXCL12 may play a major role in the etiology of benign proliferative disease in the context of an aging tissue microenvironment.
Begley
Lesa A
LA
Department of Urology and the Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109.
MacDonald
James W
JW
Department of Urology and the Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109.
Day
Mark L
ML
Department of Urology and the Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109.
Macoska
Jill A
JA
Department of Urology and the Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan 48109. Electronic address: jcoska@umich.edu.
D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000502:physiology*; D051766:Early Growth Response Protein 1 / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000502:physiology; D008297:Male; D011467:Prostate / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human