Telomerase activity and genetic alterations in primary breast carcinomas.
It has been proposed that the structural and numerical chromosome abnormalities recorded in breast cancer could be the result of telomere dysfunction and that telomerase is activated de novo to provide a survival mechanism curtailing further chromosomal aberrations. However, recent in vivo and in vitro data show that the ectopic expression of telomerase promotes tumorigenesis via a telomere length-independent mechanism. In this study, the relation between telomerase expression and the extent of chromosomal aberrations was investigated in 62 primary breast carcinomas. Telomerase activity was measured using a polymerase chain reaction-based telomeric repeat amplification protocol assay and 92% of the tumors were found to express telomerase with a relative activity ranging from 0 to 3839.6. Genetic alterations were determined by G-banding and comparative genomic hybridization analysis and 97% of the tumors exhibited chromosomal aberrations ranging from 0 to 44 (average: 10.98). In the overall series, the relationship between telomerase activity levels and genetic changes could be best described by a quadratic model, whereas in tumors with below-average genetic alteration numbers, a significant positive association was recorded between the two variables (coefficient=0.374, P=.017). The relationship between telomerase activity levels and the extent of genetic alteration may reflect the complex effect of telomerase activation upon tumor progression in breast carcinomas.
Papadopoulou
Anna
A
Department of Genetics, Saint Savas Hospital, Athens, Greece.
Trangas
Theoni
T
Teixeira
Manuel R
MR
Heim
Sverre
S
Dimitriadis
Euthimios
E
Tsarouha
Haroula
H
Andersen
Johan A
JA
Evangelou
Evangelos
E
Ioannidis
Panayiotis
P
Agnantis
Niki J
NJ
Pandis
Nikos
N
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D003582:Cytogenetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D019098:Telomerase / Q000378:metabolism*; D013997:Time Factors
D019098:Telomerase