Tumoral expression of BRCA1, estrogen receptor alpha and ID4 protein in patients with sporadic breast cancer.
BACKGROUND
BRCA1 expression is downregulated in a third of sporadic breast cancers (SBC). Most of the tumors in which BRCA1 function is diminished do not express estrogen receptor alpha (ER). Recent studies suggest that the inhibitor of DNA binding (ID)-4 could participate in the hormonal regulation of BRCA1 expression.


OBJECTIVE
To study the relationship between tumoral expression of BRCA1, ER and ID4 in SBCs.


METHODS
Forty patients with pathologic confirmation of SBC were included in this study. The mRNA expression of BRCA1, ER and ID4, determined by reverse transcription and polymerase chain reaction (RT-PCR), was correlated with the expression of gliceraldehid-3-phosphate-dehydrogenase (GAPDH). The results were analyzed using two-sided nonparametric tests (Chi-square and Spearman's rank correlation test) with alpha < 0.05.


RESULTS
Most of the tumors that expressed BRCA1 mRNA were ER-positive (p < 0.0001). In addition, a positive correlation was observed between the level of expression of these mRNAs (rs = 0.75 95% CI = 0.57-0.86; p < 0.0001). An inverse association was observed between the mRNA expression of BRCA1 and ID4 (p = 0.024) and a negative correlation between their levels of expression (rs = -0.35 95% CI -0.59 a -0.04; p = 0.028). Moreover, a negative correlation was stated between the level mRNAs of ER and ID4 (rs = - 0.45 95% CI -0.66 a -0.16; p = 0.0039).


CONCLUSIONS
In this study we demonstrate an association between the tumoral expression of BRCA1, ER and ID4 in patients with SBC. These results are in concordance with previous studies, however, to our knowledge, no other reports have described a relationship between the expression of ID4 and ER at the mRNA level in human breast cancers. These results suggest that ID4 participates in the molecular events that regulate BRCA1 and ER expression, suggesting its role as a tumor marker or potential therapeutic target.
Roldán
Gloria
G
Department of Clinical Oncology, Clinical Hospital of the University of Uruguay, Uruguay. gloriaro@cancerboard.ab.ca
Delgado
Lucía
L
Musé
Ignacio Miguel
IM
D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019313:BRCA1 Protein; D047628:Estrogen Receptor alpha; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D012333:RNA, Messenger