The role of RhoC in growth and metastatic capacity of melanoma.
BACKGROUND
RhoC overexpression in tumor cells promotes invasive and metastatic behavior. RhoC expression levels have been correlated with tumor progression and metastasis in multiple human cancers. In melanoma, RhoC is upregulated in highly metastatic tumors. Induced expression in melanoma cell lines resulted in invasion and metastasis, whereas inhibition of RhoC reversed the metastatic phenotype both in vitro and in vivo.


METHODS
RhoC mRNA and protein expression in two human melanoma cell lines (DX3aza and MeWo) and pooled primary melanocytes were investigated by means of real-time quantitative polymerase chain reaction and western blotting. RhoC protein expression was evaluated in 123 primary cutaneous melanoma samples by the use of immunohistochemistry and correlated with known prognostic features.


RESULTS
RhoC upregulation was observed in the highly metastatic DX3aza cell line, whereas in MeWo, only low expression levels could be detected. RhoC expression in primary cutaneous melanoma was strongly associated with thicker and ulcerated tumors. RhoC expression was associated with the presence of lymphatic metastases at the time of diagnosis and shorter disease-free and overall survival rates, without being an independent predictor.


CONCLUSIONS
These results further support a role for RhoC in growth and metastasis of melanoma.
Boone
Barbara
B
Dermatology Research Unit, Department of Dermatology, Ghent University Hospital, Ghent, Belgium. barbara.boone@ugent.be
Van Gele
Mireille
M
Lambert
Jo
J
Haspeslagh
Marc
M
Brochez
Lieve
L
D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000075024:rhoC GTP-Binding Protein
D012333:RNA, Messenger; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein