[Expression of antisense telomerase genes suppressing human cancer malignant phenotypes].
OBJECTIVE
Altering the expression of telomerase genes hTRT and hTR to induce changes in cancer cell biology and to determine their value in cancer gene therapy.


METHODS
By genetic transfection of antisense hTRT into HeLa cells, and treatment of PG cells with antisenes hTR oligonucleotides, their effects on cancer cell growth and malignant phenotypes were analyzed.


RESULTS
The vehicle for eukaryotic expression of hTRT antisense was constructed and transfected into HeLa cells. The obtained transfectants T4, T5 that could produce antisense hTRT stablely showed marked decrease in growth, with an arrest rate of 24%; the presence of contact growth inhibition was obvious; in nude mice transplantation, the rate for tumor induction was decreased from 100% to 25% or 0%; histologically, the tumor cells from inoculation of transfectant showed less nuclear chromatins and fewer giant tumor cells than those of the parent HeLa cells;the expression of PCNA was significantly reduced in the transfected cells. Treatment of antisense hTR oligonucleotides inhibited PG cell growth at a rate of 8%.


CONCLUSIONS
Antisense expression of telomerase genes could significantly suppress cancer cell growth, decrease malignant phenotypes and histological atypia. Therefore, altering expression of telomerase genes may be a new pathway for cancer therapy.
Yuan
X
X
Department of Pathology, Beijing Medical University, Beijing 100083.
Zhang
B
B
Ying
J
J
Wang
H
H
Zhang
H
H
Hou
L
L
Wu
B
B
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D019098:Telomerase / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D019098:Telomerase