Proteomic investigation of glioblastoma cell lines treated with wild-type p53 and cytotoxic chemotherapy demonstrates an association between galectin-1 and p53 expression.
Global protein analysis of treated and untreated glioblastoma cell lines was performed. Proteomic analysis revealed the identity of proteins that were significantly modulated by the treatment with wild-type TP53 and the cytotoxic chemotherapy SN38. In particular, galectin-1 was found to be negatively regulated by transfection with TP53 and further down-regulated by SN38. Expression level changes were confirmed by Western blot. Subsequent analysis of several high-grade glioma cell lines demonstrated very high levels of galectin-1, regardless if the cell lines contained mutant or wild-type TP53. High expression of galectin-1 in a human orthotopic murine tumor model was also detected by immunohistochemistry and revealed a consistent pattern of preferential expression in peripheral or leading tumor edges. Further examination of galectin-1 expression through microarray analysis in tumor materials from patients confirmed galectin-1 as a valuable biomarker and possible therapeutic target. These results demonstrate the utility of using proteomic approaches to interrogate and identify potential useful targets for cancer therapy by evaluating specific tumor responses, either positive or negative, to various therapies.
Puchades
Maja
M
Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, SU/Mölndal, SE-43180 Mölndal, Sweden.
Nilsson
Carol L
CL
Emmett
Mark R
MR
Aldape
Kenneth D
KD
Ji
Yongjie
Y
Lang
Frederick F
FF
Liu
Ta-Jen
TJ
Conrad
Charles A
CA
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015153:Blotting, Western; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D015180:Electrophoresis, Gel, Two-Dimensional; D037483:Galectin 1 / Q000235:genetics* / Q000302:isolation & purification; D015316:Genetic Therapy; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D013058:Mass Spectrometry; D009368:Neoplasm Transplantation; D040901:Proteomics / Q000379:methods*; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000302:isolation & purification
D000970:Antineoplastic Agents; D037483:Galectin 1; D016159:Tumor Suppressor Protein p53