Analysis of Telomeric Repeats and Telomerase Activity in Human Colon Carcinoma Cells with Gene Amplification

Bolzán, Alejandro D.; Pàez, Gerardo L.; Bianchi, Martha S.; Bianchi, Néstor O.

doi:10.1016/s0165-4608(00)00209-0

Cited by 9 publications

(5 citation statements)

References 15 publications

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“…The mean TRF lengths for KS, BCC, and SCC were determined to be 12.1, 12.6, and lOA kb for KS, Bee, and see, respectively). However, many studies have indicated that there is apparently no significant relationship between telomerase status and the size of telomere lengths (21)(22)(23).…”

Section: Resultsmentioning

confidence: 99%

Telomerase Activity in Kaposi's Sarcoma, Squamous Cell Carcinoma, and Basal Cell Carcinoma

Chen¹,

Smith

Skelton³

et al. 2001

Exp Biol Med (Maywood)

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Patients with acquired Immune deficiency syndrome (AIDS) often develop Kaposi's sarcoma (KS), an unusual skin tumor. The malignant nature of KS has long been disputed. Telomerase activity that maintains telomere length and ensures chromo-Somal stability, a frequently appearing marker In human malignancies, has been proposed to playa critical role in supporting Continued cell growth, hence formation of tumors. We examined telomerase activity in tissue extracts from 22 KS, 10 squamous cell carcinoma (SCC), and 22 basal cell carcinoma (BCC) Using the telomerlc repeat amplification protocol (TRAP). All of the tumor tissues were previously cryopreserved at _80°C. In this study, all tumor samples tested were positive for telomerase activity. Consistent with the presence of the enzyme activity, the skin tumors had relatively long telomeres. Inhibitors in the tissue extracts of some samples needed to be diluted or extracted by phenol before the enzyme activity was detected In the TRAP assay. All KS as well as two other skin carcinoma samples revealed positive telomerase activity. Our finding supports telomerase's role in tumor cell immortality and suggests the true neoplastic nature of KS.

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Section: Resultsmentioning

confidence: 99%

Telomerase Activity in Kaposi's Sarcoma, Squamous Cell Carcinoma, and Basal Cell Carcinoma

Chen¹,

Smith

Skelton³

et al. 2001

Exp Biol Med (Maywood)

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“…Only 1.46 Ϯ 0.07 lesions/kbp/M were found in the motif-poor c-Myc ORI domain. It needs to be emphasized that COLO320 DM cells have massive genetic rearrangements, which include ϳ30 -50-fold amplification of c-Myc sequences (33). The regional density of bizelesin adducts in c-Myc MAR domains is similar in COLO320DM and CEM cells (2.73 Ϯ 0.12 and 2.13 Ϯ 0.52 lesions/kbp/M, respectively).…”

Section: For Details)mentioning

confidence: 97%

AT-rich Islands in Genomic DNA as a Novel Target for AT-specific DNA-reactive Antitumor Drugs

Woynarowski¹,

Treviño²,

Rodriguez³

et al. 2001

Journal of Biological Chemistry

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Interstrand cross-links at T(A/T) 4 A sites in cellular DNA are associated with hypercytotoxicity of an anticancer drug, bizelesin. Here we evaluated whether these lethal effects reflect targeting critical genomic regions. An in silico analysis of human sequences showed that T(A/T) 4 A motifs are on average scarce and scattered. However, significantly higher local motif densities were identified in distinct minisatellite regions (200 -1000 base pairs of ϳ85-100% AT), herein referred to as "AT islands." Experimentally detected bizelesin lesions agree with these in silico predictions. Actual bizelesin adducts clustered within the model AT island naked DNA, whereas motif-poor sequences were only sparsely adducted. In cancer cells, bizelesin produced high levels of lesions (ϳ4.7-7.1 lesions/kilobase pair/M drug) in several prominent AT islands, compared with markedly lower lesion levels in several motif-poor loci and in bulk cellular DNA (ϳ0.8 -1.3 and ϳ0.9 lesions/kilobase pair/M drug, respectively). The identified AT islands exhibit sequence attributes of matrix attachment regions (MARs), domains that organize DNA loops on the nuclear matrix. The computed "MAR potential" and propensity for supercoiling-induced duplex destabilization (both predictive of strong MARs) correlate with the total number of bizelesin binding sites. Hence, MAR-like ATrich non-coding domains can be regarded as a novel class of critical targets for anticancer drugs.

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“…The activity is controlled by CST-complex ( Chen and Lingner, 2013 ), which after the G-rich strand extension, displaces telomerase, remove secondary structures, and recruit the DNA polymerase α/primase complex to synthesize the C-rich strand ( Diede and Gottschling, 1999 ; Qi and Zakian, 2000 ; Aksenova and Mirkin, 2019 ). Thus, the absence of telomerase activity in somatic cells leads to a decrease in telomeric repeat number in each cell cycle, promoting cell senescence ( Kolquist et al , 1998 ; Bolzán et al, 2000 ; Hines et al, 2005 ).…”

Section: Telomere Length Maintenance Mechanismsmentioning

confidence: 99%

Telomere organization and the interstitial telomeric sites involvement in insects and vertebrates chromosome evolution

et al. 2022

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Telomere has a central role in chromosomal stability events. Chromosome ends organized in telomere-loop prevent activation of DNA damage response (DDR) mechanisms, thus keeping the chromosome structure organized. On the other hand, free chromosome ends, dysfunctional telomeres, and interstitial telomeric sequences (ITS) can trigger chromosome rearrangements. Here, the telomere organization, function, and maintenance mechanisms, in addition to ITS types and their involvement in chromosome changes, were revisited. Despite a general (TTAGGG) n sequence being present in vertebrate telomeres, insects show more diversification of their telomere motif. The relation between ITS and chromosome rearrangements was observed in insects and vertebrates, demonstrating different types of genome organization and distribution. Some ITS cannot be considered relicts of chromosome rearrangements because probable they were inserted during a double-strand break repair mechanism. On the other hand, the involvement of telomere sequences participating or triggering chromosome rearrangements or organizing satellite DNA components in several species groups is evident. The genomic assembling advances and applying other methodologies over ITS, and their flanking regions, can help to understand the telomere participation in the chromosomal evolution in species groups with highly diversified karyotypes.

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Analysis of Telomeric Repeats and Telomerase Activity in Human Colon Carcinoma Cells with Gene Amplification

Cited by 9 publications

References 15 publications

Telomerase Activity in Kaposi's Sarcoma, Squamous Cell Carcinoma, and Basal Cell Carcinoma

Telomerase Activity in Kaposi's Sarcoma, Squamous Cell Carcinoma, and Basal Cell Carcinoma

AT-rich Islands in Genomic DNA as a Novel Target for AT-specific DNA-reactive Antitumor Drugs

Telomere organization and the interstitial telomeric sites involvement in insects and vertebrates chromosome evolution

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