Growth-related oncogene (GRO), a member of the CXC chemokine subfamily, plays a 
major role in inflammation and wound healing. CXC chemokines have been found to 
be associated with tumorigenesis, angiogenesis, and metastasis. Although 
elevated expression of GRO has been reported in several human cancers, the 
expression and role of GRO and its receptor, CXCR2, in esophageal cancer are 
poorly understood. This study used real-time reverse transcription-PCR (RT-PCR) 
and immunohistochemical approaches to show that GROalpha, GRObeta, and CXCR2 are 
up-regulated in esophageal tumor tissue. Furthermore, GROalpha, GRObeta, and 
CXCR2 are constitutively expressed in WHCO1, an esophageal cancer cell line that 
was used as a model system here. GRObeta enhances transcription of EGR-1, via 
the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, which can be 
blocked by a specific antagonist of CXCR2 (SB 225002) or specific antibody to 
GRObeta. WHCO1 cells treated with SB 225002 exhibited a 40% reduction in cell 
proliferation. A stable WHCO1 GROalpha RNA interference (RNAi) clone displayed a 
43% reduction in GROalpha mRNA levels as determined by real-time RT-PCR, reduced 
levels of GROalpha by fluorescence microscopy, and a 60% reduction in the levels 
of phosphorylated ERK1/2. A stable clone expressing GRObeta RNAi displayed >95% 
reduction in GRObeta mRNA levels, reduced levels of GRObeta by fluorescence 
microscopy, and an 80% reduction in the levels of phosphorylated ERK1/2. 
Moreover, these GROalpha RNAi- and GRObeta RNAi-expressing clones displayed a 
20% and 50% decrease in cell proliferation, respectively. Our results suggest 
that GROalpha-CXCR2 and GRObeta-CXCR2 signaling contributes significantly to 
esophageal cancer cell proliferation and that this autocrine signaling pathway 
may be involved in esophageal tumorigenesis.