Relative expression of human telomerase catalytic subunit (hTERT) transcripts in astrocytic gliomas.
Human telomerase catalytic subunit (hTERT) expression has been reported as a marker for malignancy in various tumor systems. The aim of the present study was to investigate the relative expression of hTERT (relhTERT) and its transcripts A+B+ (contained in the full-length product), Adel and Bdel in astrocytic gliomas (grades I-IV, n=38). relhTERT was assessed by duplex reverse transcription-PCR and the expression profile of Adel, Bdel and A+B+ transcripts by nested real time-PCR. relhTERT and A+B+ presence correlated well with each other ( P<0.001) and with histological grading [grades I-II (low) vs III-IV (high), P(relhTERT)=0.002 and P(A+B+)<0.001]. A+B+ was detected in one out of seven hTERT-positive low-grade tumors, while it was present in 96.3%, and predominantly expressed in 59.3% of high-grade tumors. Bdel predominance was observed only in three cases, irrespective of grading, while Bdel levels equal or close to those of A+B+ were found in 30.4% of grade IV tumors. In situ hybridization with specific Bplus and Bdel probes revealed positive signals for both mRNAs in association with relhTERT and respective variant profiles. In addition, this method was useful in assessing hTERT expression in cases where sampling errors for RT-PCR were unavoidable. Our findings show that except for differences in relhTERT, low- and high-grade astrocytic gliomas exhibit distinct hTERT variant profiles, most of which seem to be in line with the role attributed to hTERT regarding its contribution to the acquisition of malignant potential during astrocyte carcinogenesis. Low-grade tumors mainly express Adel and Bdel. High-grade tumors, especially grade IV, always express A+B+, mostly but not always in predominance over Adel and Bdel. In this same group, profiles with Bdel predominance or relatively equal A+B+/Bdel expression are also observed, and Adel is often missing. Whether these differences characterize tumors with different biological behavior remains to be elucidated.
Kotoula
V
V
Department of Pathology and Department of Medical Physics, Medical School, Auth, 540 06 Thessaloniki, Greece.
Barbanis
S
S
Nikolakaki
E
E
Koufoyannis
D
D
Papadimitriou
C S
CS
Karkavelas
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000502:physiology; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics; D020134:Catalytic Domain / Q000502:physiology; D002648:Child; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase