c-Myb and Bcl-x overexpression predicts poor prognosis in colorectal cancer: clinical and experimental findings.
The aim of this study was twofold: to assess the relationship between c-Myb and Bcl-x expression and to evaluate the prognostic significance of their expression in colorectal carcinoma (CRC) patients. Analysis of tumors from 91 CRC patients for expression of c-Myb and Bcl-x revealed a significant relationship between these two proteins. Kaplan-Meier's analysis showed an increased risk of relapse and death in patients whose tumor specimens displayed high c-Myb levels and Bcl-x positivity. Similar results were also observed excluding Dukes' D patients. Molecular analysis using three c-Myb-overexpressing LoVo clones indicated that c-Myb overexpression was accompanied by up-regulation of Bcl-x(L) protein and mRNA. Tumors originating from these clones injected in nude mice were significantly larger than those formed in mice injected with parental or vector-transfected LoVo cells. Moreover, tumors derived from parental and control vector-transfected but not from c-Myb-overexpressing LoVo cells showed high frequency of apoptotic cells. These results provide direct evidence of an association between c-Myb and Bcl-x expression and suggest that expression of both molecules might be a useful prognostic marker in CRC.
Biroccio
A
A
Experimental Chemotherapy Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158, Rome, Italy.
Benassi
B
B
D'Agnano
I
I
D'Angelo
C
C
Buglioni
S
S
Mottolese
M
M
Ricciotti
A
A
Citro
G
G
Cosimelli
M
M
Ramsay
R G
RG
Calabretta
B
B
Zupi
G
G
D002277:Carcinoma / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000502:physiology; D003110:Colonic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012004:Rectal Neoplasms / Q000473:pathology / Q000503:physiopathology*; D016019:Survival Analysis; D014162:Transfection; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D051020:bcl-X Protein