References

Notes: Laboratory of Molecular Cell Biology, Kanagawa Cancer Center Research Institute, Yokohama, Japan 0950-9232 ENGLISH ENGLAND Telomerase activity is found in most cancer tissues and many immortalized cell lines as well as in germ line cells but it is generally undetected in normal human somatic tissues. There is weak telomerase activity in some cell types of hematopoietic lineage in which a stem cell-like subpopulation may exist. Likewise, physiologically regenerating somatic tissues and organs such as skin, small intestine, and most other epithelia of the human body are supposed to contain similar cell lineages to maintain their renewal throughout the life span of individuals. It is therefore of interest whether telomerase activity is present in physiologically regenerating epithelial cells. Telomerase activity was detected, though very weakly, in cultured normal epidermal keratinocytes and at higher levels in a subpopulation that adhere rapidly on collagen IV-coated culture dishes. No telomerase activity was detected in a subpopulation that was less adherent on the coated dishes. The rapidly adherent subpopulation of keratinocytes was enriched in small proliferating cells with macrocolony forming potential. It was also passaged through more generations in culture, and expressed integrin beta 1 at higher levels than the less adherent subpopulation. Telomerase activity was similarly found in ectocervical keratinocytes as well as in simple endocervical epithelial cells. These findings provide the evidence of a telomerase-positive population among physiologically regenerating normal human epithelial cells. The identity of the telomerase- positive cells remains to be defined JOURNAL-ARTICLE EC 2.7.7.-; 9007-34-5 96313280 9611
Reference ID: 4906

Notes: The terminal differentiation of epithelial keratinocytes has been proposed to be a specialized form of programmed cell death (apoptosis). We examined the time correlation of apoptosis and terminal differentiation by human ectocervical keratinocytes in a suspension culture that induces either of these events in epithelial cells. We found that a loss of cell anchorage did not result in the immediate onset of apoptotic DNA degradation but sensitized the cells to that triggered by calcium. This susceptibility appeared in parallel with the irreversible loss of growth potential and the accumulation of involvucrin, suggesting that the ectocervical keratinocytes in suspension become cometent to calcium-inducible apoptosis as they committed to terminal differentiation. Cycloheximide, which inhibited the calcium induction of DNA fragmentation, was also inhibitory to teminal differentiation. These correlations support the notion that terminal differentiation of keratinocytes couples with apoptosis. Apoptosis seemed to be independent of p53 because it was down-regulated in suspension cultures of ectocervical keratinocytes.
Reference ID: 4925

Notes: Department of Gynecology, Nippon Medical School, Tokyo 0910-5050 ENGLISH JAPAN We have established two distinct human cervical cell lines, NCC16 and NCE16, after transfecting human papillomavirus type 16 (HPV16) DNA into normal human endo-cervical and ecto-cervical epithelial cells, respectively. Both lines expressed HPV16 E6 and E7 as detected by reverse transcriptase-polymerase chain reaction and northern blot hybridization. These cells have been passaged for over 100 population doublings and express strong telomerase activity. Neither cell line was tumorigenic in athymic nu/nu mice. However, both NCC16 and NCE16 developed abnormally stratified architectures following implantation with a silicon membrane sheet in the back of athymic nude mice. The former cells were pathohistologically similar to carcinoma, while the latter produced Alcian-blue positive cells, suggesting the occurrence of metaplastic changes. These distinct cell lines offer a useful model system for the study of cervical carcinogenesis and of its regulatory mechanism after HPV infection in different regions of the uterine cervix JOURNAL-ARTICLE EC 2.7.7.-; 0 97455925 9712
Reference ID: 4900

Notes: It has been ten years after the suggestion that the human papillomavirus type 16(HPV16) may cause cancer. Two onco genes E6 and E7 were foud and structures and functions of these genes have been analyzed since then. Along these researches targets of these two oncogene products have been identified to be p53 and Rb proteins. Both of the p53 and the Rb genes are konwn as tumor suppressor genes. From these results mechanisms of tumor induction by the HPV16 can be extended to more common interest not only to the virus function itself. Now further understanding of the HPV16 is in progress becuase the virus may cause the interfering cell cycle of human cells. [Review article in Japanese]
Reference ID: 4939

Notes: [Review article in Japanese]
Reference ID: 4940

Notes: Paper is written in Japanese. Abstruct: Telomeres are specialized structures at the ends of eukaryotic chromosomes consisting of simple repeated DNA sequences, and in humans they are composed of l0-15 kilobases of TTAGGG repeats. Telomere erosion, approximately of 50-200 bps, occurs with each round of DNA replication by the mechanism of end replication problem, and shortening of telomere length to less than 2,5 kb appears to be critical for cellular crisis. These telomeric repeats are elongated by telomerase, a ribonucleoprotein enzyme that extends the 3' end of telomeres, and it has been shown that most Immortalized cells and cancer cells have telomerase activities. In the present study, we analyzed the telomere lengths and telomerase activities of human epithelial cells transfected with HPV16 and SV40 tumor virus oncogenes to clarify the relationship between immortalizaion and telomerase activation. Our results demonstrated a marked shortening of telomere in HPV16-transformed cells, which gradually extended during subsequent passages. Strong telomerase activities were stably maintained durlng these passages. By contrast, SV40-transfected cells had long telomere, but telomerase activities were not detected in this cell line. Telomere length of this transformant decreased along with passages, and the telomerase activities for the first time appeared in 2 among 9 clones of these cells at the 6th passage (31 population doublings) , the timing of which was synchronous with cellular crisis. Later, all the clones showed high levels of telomerase activity. These observations suggested that telomerase-positive clones appeared in earlier stage and then became dominant in the population of this cell line. From these results it is likely that the two types of similar DNA tumor virus transformed human epithelial cells in different modes.
Abstract: Journal published by the Yokohama City University.
Reference ID: 5945