Relationships of P53 and Bak with EPO and EPOR in human colorectal cancer.
BACKGROUND
EPO (erythropoietin) counteracts p53-dependent apoptosis. EPO, which acts via its receptor EPOR, protects cells and inhibits apoptosis in normal cells and some cancer tissues by severe down-regulation of Bak. We aimed to investigate the relationship between p53 and Bak expression and EPO and EPOR in human colorectal carcinomas.


METHODS
The expression of p53 was compared with Bak, EPO and EPOR in 96 colorectal carcinomas by means of immunohistochemistry.


RESULTS
Purely nuclear p53 was significantly higher expressed in the moderately differentiated cancers in comparison with the poorly differentiated ones (p=0.007). P53 expression did not correlate with cytoplasmic markers: Bak, EPO and EPOR, but EPO and EPOR were significantly associated with Bak expression (p<0.001, r=0.524 and p<0.001, r=0.455, respectively). p53 expression was not associated with disease-free survival during the 3 years and 9 months long follow-up.


CONCLUSIONS
A complete disruption of association between p53 and Bak could impair of p53-dependent apoptotic pathway that involves Bak. The relationship of Bak with EPO and EPOR is evidence of their co-expression suggesting competition between EPO mediated cell survival and Bak associated apoptosis in colorectal carcinomas.
Department of General, Medical University of Bialystok, Waszyngtona St 13, 15-269 Bialystok, Poland.
Marek
M
Baltaziak
Mariusz
M
Koda
Andrzej
A
Wincewicz
Mariola
M
Sulkowska
Luiza
L
Kanczuga-Koda
Stanislaw
S
Sulkowski
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D018572:Disease-Free Survival; D004921:Erythropoietin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis / Q000378:metabolism*
C494772:BAK1 protein, human; D017467:Receptors, Erythropoietin; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050998:bcl-2 Homologous Antagonist-Killer Protein; D004921:Erythropoietin