Possible immortalization of Hodgkin and Reed-Sternberg cells: telomerase expression, lengthening of telomere, and inhibition of apoptosis by NF-kappaB expression.
Telomerase, an enzyme associated with cellular immortality, is expressed on malignant tumor cells. Deregulation of telomerase is thought to facilitate tumorigenesis and cellular immortality by providing cancer cells with unlimited proliferation capacity. Hodgkin and Reed-Sternberg (H&RS) cells are generally considered as neoplastic cells in Hodgkin's disease (HD), however, such cells are only found in a minority of HD lesions. In addition, H&RS cells with mitotic features are rare and mummified forms are occasionally encountered. There are no available data on the relationship between telomerase activity and apoptosis in HD. We studied 14 cases with Hodgkin's disease (mixed cellularity type, nine cases; nodular sclerosis type, five cases) to clarify the relationship between telomerase activity and apoptosis using in situ hybridization of human telomerase reverse transcriptase (hTERT), reverse transcriptase-polymerase chain reaction (RT-PCR) of hTERT, using extracted RNA and immunohistochemistry of nuclear factor-?B (NF-?B), and TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) technique for apoptosis. We also analyzed the telomere length, using sorted H&RS cells. TUNEL showed a few apoptotic H&RS cells, but the cells frequently expressed hTERT, as confirmed by ISH and RT-PCR. Lengthening of the telomere of H&RS cells was noted in ten cases. In addition, H&RS cells frequently expressed NF-?B, which is known as an inducible transcription factor and inhibitor of apoptosis. Our findings of telomerase activity in H&RS cells indicate that these cells are neoplastic and are potentially immortal. In addition, NF-?B expression on H&RS cells suggests its possibility in inhibition of apoptosis of these cells.
Ohshima
K
K
Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan.
Sugihara
M
M
Haraoka
S
S
Suzumiya
J
J
Kanda
M
M
Kawasaki
C
C
Shimazaki
K
K
Kikuchi
M
M
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D002648:Child; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D006689:Hodgkin Disease / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D016539:Reed-Sternberg Cells / Q000737:chemistry / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D004268:DNA-Binding Proteins; D016328:NF-kappa B; C422952:telomerase RNA; D012313:RNA; D004247:DNA; D019098:Telomerase