Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient
Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancersuppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral o...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-05-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558604800733 |
| _version_ | 1818938689298890752 |
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| author | Nicholas R. Forsyth Carmela P. Morales Shirish Damle Bruce Boman Woodring E. Wright Levy Kopelovich Jerry W. Shay |
| author_facet | Nicholas R. Forsyth Carmela P. Morales Shirish Damle Bruce Boman Woodring E. Wright Levy Kopelovich Jerry W. Shay |
| author_sort | Nicholas R. Forsyth |
| collection | DOAJ |
| description | Normal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancersuppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, E6/E7) can lead to escape from senescence, additional doublings, entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the spontaneously immortalized derivative (C26Ci) cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention. |
| first_indexed | 2024-12-20T06:11:51Z |
| format | Article |
| id | doaj.art-35093c4373e54c6db4a8893144e09c71 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-20T06:11:51Z |
| publishDate | 2004-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-35093c4373e54c6db4a8893144e09c712022-12-21T19:50:39ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022004-05-016325826510.1593/neo.04103Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis PatientNicholas R. Forsyth0Carmela P. Morales1Shirish Damle2Bruce Boman3Woodring E. Wright4Levy Kopelovich5Jerry W. Shay6Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USADivision of Genetic and Preventive Medicine, Thomas Jefferson University, Philadelphia, PA, USADivision of Genetic and Preventive Medicine, Thomas Jefferson University, Philadelphia, PA, USADivision of Genetic and Preventive Medicine, Thomas Jefferson University, Philadelphia, PA, USADivision of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892, USADepartment of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USANormal human diploid cells do not spontaneously immortalize in culture, but instead enter replicative senescence after a finite number of population doublings. Ablation of key checkpoint arrest or cancersuppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, E6/E7) can lead to escape from senescence, additional doublings, entrance into crisis phase, where immortal clones emerge at low frequency. In the vast majority of cases, telomerase is reactivated and telomeres are stabilized. Here we describe the spontaneous immortalization of clinically normal fibroblasts derived from colonic stroma of a familial adenomatous polyposis (FAP) patient. The preimmortal (C26C) and the spontaneously immortalized derivative (C26Ci) cells are heterozygous for a characterized germline mutation in exon 15 of the adenomatous polyposis coli gene. Immortalization was accompanied by spontaneous reactivation of endogenous telomerase and establishment of telomeres at presenescent lengths. Normal checkpoint behavior is retained and a diploid karyotype is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.http://www.sciencedirect.com/science/article/pii/S1476558604800733Adenomatous polyposis colifamilial adenomatous polyposisspontaneous immortalizationtelomerasetelomere |
| spellingShingle | Nicholas R. Forsyth Carmela P. Morales Shirish Damle Bruce Boman Woodring E. Wright Levy Kopelovich Jerry W. Shay Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient Neoplasia: An International Journal for Oncology Research Adenomatous polyposis coli familial adenomatous polyposis spontaneous immortalization telomerase telomere |
| title | Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient |
| title_full | Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient |
| title_fullStr | Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient |
| title_full_unstemmed | Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient |
| title_short | Spontaneous Immortalization of Clinically Normal Colon-Derived Fibroblasts from a Familial Adenomatous Polyposis Patient |
| title_sort | spontaneous immortalization of clinically normal colon derived fibroblasts from a familial adenomatous polyposis patient |
| topic | Adenomatous polyposis coli familial adenomatous polyposis spontaneous immortalization telomerase telomere |
| url | http://www.sciencedirect.com/science/article/pii/S1476558604800733 |
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