Telomerase activity and expression of telomerase RNA component and telomerase catalytic subunit gene in cervical cancer.
Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component (hTR) and the telomerase catalytic subunit gene (hTERT) product, has been shown to be activated in the majority of cancer tissues and immortalized cells. To study telomerase activation during the progression of cervical cancer, the expression of hTR and hTERT RNAs in tissues of various stages of cervical cancer was analyzed using the in situ hybridization method and compared with proliferative activity as estimated by Ki-67 immunostaining. To test whether expression of these components is reflected in enzyme activity, we determined the levels of the RNAs in cervical cancer and normal tissues and in primary and immortal keratinocytes by reverse transcription-polymerase chain reaction and RNase protection assays and compared the results to telomerase activities as detected by telomeric repeat amplification protocol assay. In situ hybridization signals of hTR and hTERT were present not only in carcinoma tissues but also in normal epidermal layers. In many adenocarcinoma and fewer squamous cell carcinoma tissues, both signals were focally increased where high proliferative activity was present at the stages of dysplasia/metaplasia, in situ carcinoma, and invasive carcinoma. The level of bTERT, as quantitated by RNase protection assay, was not different between cancer and control tissues or immortal and a subset of primary keratinocytes and did not correlate with telomerase activity. These results indicate that expression of hTR and bTERT is up-regulated in at least a subset of neoplastic cells at an early stage of carcinogenesis and that unidentified factors, such as the modulation or coordination of its protein level with other products, may contribute to the activation of telomerase in cervical cancer.
Nakano
K
K
Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 19024, USA.
Watney
E
E
McDougall
J K
JK
D002455:Cell Division; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D022661:RNA, Untranslated; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology
D017931:DNA Primers; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D011506:Proteins; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm; D022661:RNA, Untranslated; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase