Telomerase activity, estrogen receptors (alpha, beta), Bcl-2 expression in human breast cancer and treatment response.
BACKGROUND
The mechanism for maintaining telomere integrity is controlled by telomerase, a ribonucleoprotein enzyme that specifically restores telomere sequences, lost during replication by means of an intrinsic RNA component as a template for polymerization. Among the telomerase subunits, hTERT (human telomerase reverse transcriptase) is expressed concomitantly with the activation of telomerase. The role of estrogens and their receptors in the transcriptional regulation of hTERT has been demonstrated. The current study determines the possible association between telomerase activity, the expression of both molecular forms of estrogen receptor (ERalpha and ERbeta) and the protein bcl-2, and their relative associations with clinical parameters.


METHODS
Tissue samples from 44 patients with breast cancer were used to assess telomerase activity using the TRAP method and the expression of ERalpha, ERbeta and bcl-2 by means of immunocytochemical techniques.


RESULTS
Telomerase activity was detected in 59% of the 44 breast tumors examined. Telomerase activity ranged from 0 to 49.93 units of total product generated (TPG). A correlation was found between telomerase activity and differentiation grade (p = 0.03). The only significant independent marker of response to treatment was clinical stage. We found differences between the frequency of expression of ERalpha (88%) and ERbeta (36%) (p = 0.007); bcl-2 was expressed in 79.5% of invasive breast carcinomas. We also found a significant correlation between low levels of telomerase activity and a lack of ERbeta expression (p = 0.03).


CONCLUSIONS
Lower telomerase activity was found among tumors that did not express estrogen receptor beta. This is the first published study demonstrating that the absence of expression of ERbeta is associated with low levels of telomerase activity.
Murillo-Ortiz
Blanca
B
Unidad de Investigacion Clinica, UMAE no, 1 Bajio, IMSS Leon Guanajuato, Mexico. bomo907@hotmail.com
Astudillo-De la Vega
Horacio
H
Castillo-Medina
Sebastian
S
Malacara
J M
JM
Benitez-Bribiesca
Luis
L
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D003520:Cyclophosphamide / Q000627:therapeutic use; D015251:Epirubicin / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism*; D016896:Treatment Outcome
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019253:Proto-Oncogene Proteins c-bcl-2; D015251:Epirubicin; D003520:Cyclophosphamide; D019098:Telomerase; D005472:Fluorouracil