Telomere Length and Telomerase Activity in Bladder and Prostate Cancer Cell Lines

Kageyama, Yukio; Kamata, Shigeyoshi; Yonese, Junji; Oshima, Hiroyuki

doi:10.1111/j.1442-2042.1997.tb00216.x

Cited by 16 publications

(11 citation statements)

References 16 publications

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“…A series of our prior studies showed short telomeres of LNCaP and DU145 cells and long telomeres of TSU-Pr1 cells [11,12]. LNCaP and DU145 cells each have a specific telomere length, which is stable regardless of cell division [14]. These findings suggest that a regulatory mechanism exists for limiting telomere elongation by high telomerase activity.…”

Section: Discussionmentioning

confidence: 77%

Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro

Soda

Raymond²,

Sharma³

et al. 2000

Prostate

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Section: Discussionmentioning

confidence: 77%

Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro

Soda

Raymond²,

Sharma³

et al. 2000

Prostate

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“…23) However, an in vitro study showed that bladder cancer cell lines expressed strong telomerase activity with long telomeres, which may, however, be an in vitro artifact. 24) In addition, prompt telomerase activation was observed in a chemical carcinogenesis model of the rat, 25) suggesting that telomerase might be activated at a phase earlier than that of telomere shortening. In view of our findings in this study, telomerase activation might be a primary event during BBN bladder carcinogenesis in the rat, and might lead to malignant conversion without frequent genetic alteration.…”

Section: Discussionmentioning

confidence: 99%

Telomerase Is Upregulated in Irreversible Preneoplastic Lesions during Bladder Carcinogenesis in Rats

Shimazui¹,

Ami²,

Miyanaga³

et al. 2002

Japanese Journal of Cancer Research

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Multiple occurrence or recurrence after transurethral resection is an important characteristic of superficial bladder tumors. To study bladder carcinogenesis, we focused on detection of telomerase activation, which was investigated in several human cancers, including bladder tumors. We experimentally examined the telomerase activity during bladder carcinogenesis, especially in precancerous lesions, induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. Male Wistar rats were given 0.05% BBN in water from the age of 8 weeks to 24 weeks. Subgroups were euthanized at 4, 8, 10, 12, 18, and 24 weeks after BBN administration. Using the stretch PCR method, telomerase activity was semiquantified in exfoliated bladder epithelial cells. In addition, telomere length in each subgroup was measured by southern hybridization for the terminal restriction fragment using a (TTAGGG) 4 probe. Statistical analyses were performed using analysis of variance and Fisher's PLSD test. Epithelial cells of normal bladder in the control groups and those of diffuse hyperplasia, which was a reversible change at 4 weeks, expressed no telomerase activity. In contrast, telomerase activity significantly increased in the stage after nodular hyperplasia, an irreversible change at 8 weeks, then elevated with carcinogenesis. However, telomere length was still preserved by the 12th week, and was shortened at 18 and 24 weeks. These results suggest that telomerase activation is probably induced independent of telomere shortening during bladder carcinogenesis in the rat, and might be a biological tumor marker of irreversible preneoplastic lesions, which evolve into bladder tumors in the rat. Key words: Bladder carcinogenesis -Telomerase -Telomere -BBN -HyperplasiaTelomerase is a ribonucleoprotein complex that synthesizes telomeric DNA and contributes to the maintenance of telomeres, which are composed of TTAGGG repeats located at the end of the chromosome and play a critical role in chromosome structure and function.1) A certain length of telomere is important for cell division; normal somatic cells express very low or undetectable levels of telomerase activity, and progressively lose their telomeric sequence via cell division. Therefore, the activation of this enzyme has been proposed to be a critical event in the immortalization of the cell, and is characteristic of most cancer cells. It has been reported that 80 to 90% of bladder tumors express telomerase activity, 2) and that the detection of telomerase activity in bladder tumor tissues and/or in exfoliated tumor cells in urine is useful as a new diagnostic tool. 3,4) To examine the critical point at which telomerase activation occurs in the course of bladder carcinogenesis, we measured telomerase activity in bladder epithelium during N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) carcinogenesis in the rat. BBN bladder carcinogenesis is thought to be a model for superficial bladder tumor. It has been well described that during bladder cancer development, diffuse hyperplasia at 4 weeks after BBN a...

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“…Contribution of telomere dysfunction to regional amplification and deletion in cancer genomes was also observed in various mammary cancer systems (O'Hagan et al, 2002). Previous studies have shown that telomerase is expressed in DU145, PC3 and LNCaP (Sommerfeld et al, 1996;Kageyama et al, 1997). However, it has been suggested that despite telomerase expression, telomere-induced anaphase bridges can still occur at a low frequency indicating an ongoing instability process (Stewenius et al, 2005).…”

Section: Bfb-dependent Telomeric Alterationsmentioning

confidence: 96%

“…Studies to date have associated the BFB cycle with telomere shortening observed in HPIN and early invasive foci of carcinoma, contributing to genomic instability and presumably a crisis-like process. However, ongoing BFB in CaP cell lines, known to express telomerase (Sommerfeld et al, 1996;Kageyama et al, 1997) suggests continuation of this CIN mechanism after immortalization. Ongoing but low-level instability via BFB could enable the tumor population to adapt better to changes in the microenvironment and account for some of the tumor heterogeneity seen at later stages of CaP progression.…”

Section: Interpretation Of Chromosomal Instability Findingsmentioning

confidence: 99%

Correlating breakage-fusion-bridge events with the overall chromosomal instability and in vitro karyotype evolution in prostate cancer

Vukovic¹,

Beheshti

Park

et al. 2007

Cytogenet Genome Res

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Chromosomal instability (CIN) is thought to underlie the generation of chromosomal changes and genomic heterogeneity during prostatic tumorigenesis. The breakage-fusion-bridge (BFB) cycle is one of the CIN mechanisms responsible for characteristic mitotic abnormalities and the occurrence of specific classes of genomic rearrangements. However, there is little detailed information concerning the role of BFB and CIN in generating genomic diversity in prostate cancer. In this study we have used molecular cytogenetic methods and array comparative genomic hybridization analysis (aCGH) of DU145, PC3, LNCaP, 1532T and 1542T to investigate the in vitro role of BFB as a CIN mechanism in karyotype evolution. Analysis of mitotic structures in all five prostate cancer cell lines showed increased frequency of anaphase bridges and nuclear strings. Structurally rearranged dicentric chromosomes were observed in all of the investigated cell lines, and Spectral Karyotyping (SKY) analysis was used to identify the participating rearranged chromosomes. Multicolor banding (mBAND) and aCGH analysis of some of the more complex chromosomal rearrangements and associated amplicons identified inverted duplications, most frequently involving chromosome 8. Chromosomal breakpoint analysis showed there was a higher frequency of rearrangement at centromeric and pericentromeric genomic regions. The distribution of inverted duplications and ladder-like amplifications was mapped by mBAND and by aCGH. Adjacent spacing of focal amplifications and microdeletions were observed, and focal amplification of centromeric and end sequences was present, particularly in the most unstable line DU145. SKY analysis of this line identified chromosome segments fusing with multiple recipient chromosomes (jumping translocations) identifying potential dicentric sources. Telomere free end analysis indicated loss of DNA sequence. Moreover, the cell lines with the shortest telomeres had the most complex karyotypes, suggesting that despite the expression of telomerase, the reduced telomere length could be driving the observed BFB events and elevated levels of CIN in these lines.

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Telomere Length and Telomerase Activity in Bladder and Prostate Cancer Cell Lines

Abstract: The presence of telomerase may be a biological character of bladder and prostate cancers as well as other malignancies, although it does not always compensate telomere shortening.

Cited by 16 publications

References 16 publications

Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro

Effects of androgens on telomerase activity in normal and malignant prostate cells in vitro

Telomerase Is Upregulated in Irreversible Preneoplastic Lesions during Bladder Carcinogenesis in Rats

Correlating breakage-fusion-bridge events with the overall chromosomal instability and in vitro karyotype evolution in prostate cancer

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