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Differential GADD45, p21CIP1/WAF1, MCL-1 and topoisomerase II gene induction and secondary DNA fragmentation after camptothecin-induced DNA damage in two mutant p53 human colon cancer cell lines.
Oncol Res. 1996; 8(7-8):317-23.OR

Abstract

Camptothecin (CPT) traps covalent DNA topoisomerase I-linked DNA single-strand breaks (cleavable complexes). To determine the differences in DNA damage signalling leading to differential sensitivity to CPT, two human colon cancer cell lines, SW620 and KM12, with nonfunctional p53 and the same level of topoisomerase I cleavable complex formation but differential sensitivity to CPT (Cancer Res. 56:4430-7; 1996) were studied. The levels of mRNA expression of DNA damage-inducible or death-related genes were measured at different times after CPT treatment. KM12 cells exhibited 3-fold higher basal levels of BCL-2 mRNA. Consistently, secondary DNA fragmentation, quantitated using a filter elution assay, was detected 24 h later and was 2-4-fold lower in KM12 cells than in SW620 cells. No induction of BAX was detected in either cell line. Consistent with the absence of functional p53, p21CIP1/WAF1 and GADD45 genes were not induced within the first 24 h. However, in SW620 cells, both mRNA levels were increased more than 10-fold at 48 h. The BCL-2-related gene MCL-1 and topoisomerase II mRNA were induced at 24 h, and topoisomerase I mRNA levels increased 3-fold at 48 h, only in SW620 cells. We conclude that cellular response to CPT-induced DNA damage can involve p53-independent pathways leading to the induction of p53-effector genes. Induction of these genes at the onset of apoptosis is associated with CPT sensitivity.

Authors+Show Affiliations

Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892-4255, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8938795

Citation

Goldwasser, F, et al. "Differential GADD45, p21CIP1/WAF1, MCL-1 and Topoisomerase II Gene Induction and Secondary DNA Fragmentation After Camptothecin-induced DNA Damage in Two Mutant P53 Human Colon Cancer Cell Lines." Oncology Research, vol. 8, no. 7-8, 1996, pp. 317-23.
Goldwasser F, Bae I, Fornace AJ, et al. Differential GADD45, p21CIP1/WAF1, MCL-1 and topoisomerase II gene induction and secondary DNA fragmentation after camptothecin-induced DNA damage in two mutant p53 human colon cancer cell lines. Oncol Res. 1996;8(7-8):317-23.
Goldwasser, F., Bae, I., Fornace, A. J., & Pommier, Y. (1996). Differential GADD45, p21CIP1/WAF1, MCL-1 and topoisomerase II gene induction and secondary DNA fragmentation after camptothecin-induced DNA damage in two mutant p53 human colon cancer cell lines. Oncology Research, 8(7-8), 317-23.
Goldwasser F, et al. Differential GADD45, p21CIP1/WAF1, MCL-1 and Topoisomerase II Gene Induction and Secondary DNA Fragmentation After Camptothecin-induced DNA Damage in Two Mutant P53 Human Colon Cancer Cell Lines. Oncol Res. 1996;8(7-8):317-23. PubMed PMID: 8938795.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential GADD45, p21CIP1/WAF1, MCL-1 and topoisomerase II gene induction and secondary DNA fragmentation after camptothecin-induced DNA damage in two mutant p53 human colon cancer cell lines. AU - Goldwasser,F, AU - Bae,I, AU - Fornace,A J,Jr AU - Pommier,Y, PY - 1996/1/1/pubmed PY - 2001/3/28/medline PY - 1996/1/1/entrez SP - 317 EP - 23 JF - Oncology research JO - Oncol Res VL - 8 IS - 7-8 N2 - Camptothecin (CPT) traps covalent DNA topoisomerase I-linked DNA single-strand breaks (cleavable complexes). To determine the differences in DNA damage signalling leading to differential sensitivity to CPT, two human colon cancer cell lines, SW620 and KM12, with nonfunctional p53 and the same level of topoisomerase I cleavable complex formation but differential sensitivity to CPT (Cancer Res. 56:4430-7; 1996) were studied. The levels of mRNA expression of DNA damage-inducible or death-related genes were measured at different times after CPT treatment. KM12 cells exhibited 3-fold higher basal levels of BCL-2 mRNA. Consistently, secondary DNA fragmentation, quantitated using a filter elution assay, was detected 24 h later and was 2-4-fold lower in KM12 cells than in SW620 cells. No induction of BAX was detected in either cell line. Consistent with the absence of functional p53, p21CIP1/WAF1 and GADD45 genes were not induced within the first 24 h. However, in SW620 cells, both mRNA levels were increased more than 10-fold at 48 h. The BCL-2-related gene MCL-1 and topoisomerase II mRNA were induced at 24 h, and topoisomerase I mRNA levels increased 3-fold at 48 h, only in SW620 cells. We conclude that cellular response to CPT-induced DNA damage can involve p53-independent pathways leading to the induction of p53-effector genes. Induction of these genes at the onset of apoptosis is associated with CPT sensitivity. SN - 0965-0407 UR - https://www.unboundmedicine.com/medline/citation/8938795/Differential_GADD45_p21CIP1/WAF1_MCL_1_and_topoisomerase_II_gene_induction_and_secondary_DNA_fragmentation_after_camptothecin_induced_DNA_damage_in_two_mutant_p53_human_colon_cancer_cell_lines_ L2 - https://antibodies.cancer.gov/detail/CPTC-TOP1-1 DB - PRIME DP - Unbound Medicine ER -