Type

Journal Article

Authors

L S Young
A D K Hill
F Bane
M McIlroy
E Hughes
C Byrne
C deBlacam

Subjects

Biochemistry

Topics
skin neoplasms rna messenger chromatin immunoprecipitation immunoenzyme techniques cell proliferation dasatinib reverse transcriptase polymerase chain reaction s 100 calcium binding protein beta subunit drug effects pyrimidines antagonists inhibitors s100 proteins tumor cells cultured humans rna small interfering homeodomain proteins hoxc11 protein human genetics drug therapy metabolism protein tyrosine kinases protein kinase inhibitors fluorescent antibody technique gene expression regulation neoplastic nerve growth factors melanoma blotting western nuclear receptor coactivator 1 immunoprecipitation thiazoles phosphorylation pharmacology

HOXC11-SRC-1 regulation of S100beta in cutaneous melanoma: new targets for the kinase inhibitor dasatinib. (2011)

Abstract Cutaneous melanoma is an aggressive disease. S100beta is an established biomarker of disease progression; however, the mechanism of its regulation in melanoma is undefined. Expression of HOXC11 and SRC-1 was examined by immunohistochemistry and immunofluorescence. Molecular and cellular techniques were used to investigate regulation of S100beta, including, western blot, qPCR, ChIP and migration assays. Expression levels of the transcription factor HOXC11 and its coactivator SRC-1 were significantly elevated in malignant melanoma in comparison with benign nevi (P<0.001 and P=0.017, respectively, n=80), and expression of HOXC11 and SRC-1 in the malignant tissue associated with each other (P<0.001). HOXC11 recruitment to the promoter of S100beta was observed in the primary melanoma cell line SKMel28. S100beta expression was found to be dependant on both HOXC11 and SRC-1. Treatment with the Src/Abl inhibitor, dasatinib, reduced HOXC11-SRC-1 interaction and prevented recruitment of HOXC11 to the S100beta promoter. Dasatinib inhibited both mRNA and protein levels of S100beta and reduced migration of the metastatic cell line MeWo. We have defined a signalling mechanism regulating S100beta in melanoma, which can be modulated by dasatinib. Profiling patients for expression of key markers of this network has the potential to increase the efficacy of dasatinib treatment.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

L S Young, A D K Hill, F Bane, M McIlroy, E Hughes, C Byrne, C deBlacam

Experts in our system

1
Leonie S Young
Royal College of Surgeons in Ireland
Total Publications: 42
 
2
Arnold D K Hill
Royal College of Surgeons in Ireland
Total Publications: 110
 
3
Fiona T Bane
Royal College of Surgeons in Ireland
Total Publications: 9
 
4
Marie McIlroy
Royal College of Surgeons in Ireland
 
5
Christopher Byrne
Royal College of Surgeons in Ireland
Total Publications: 13