Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient

Nicholas R. Forsyth, Carmela P. Morales, Shirish Damle, Bruce Boman, Woodring E. Wright, Levy Kopelovich, Jerry W. Shay

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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 cancer-suppressor genes, through dominantly inherited germline mutation (p53+/-, Li-Fraumeni) or viral oncogene expression (SV40 large T, HPV16/18, and E6/E7) can lead to escape from senescence, additional doublings, and 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 karyo-type is maintained. These cells provide a valuable new addition to the limited number of spontaneously immortalized human cell types, particularly fibroblast cells, and will be useful in experimentally determining the functional pathways in neoplastic development and in the identification of potential molecular targets for cancer chemoprevention.

Original languageEnglish (US)
Pages (from-to)258-265
Number of pages8
JournalNeoplasia
Volume6
Issue number3
StatePublished - May 2004

Fingerprint

Adenomatous Polyposis Coli
Colon
Fibroblasts
Germ-Line Mutation
Telomerase
Telomere
Diploidy
APC Genes
Cell Aging
Chemoprevention
Tumor Suppressor Genes
Oncogenes
Exons
Clone Cells
Population
Neoplasms

Keywords

  • Adenomatous polyposis coli
  • Familial adenomatous polyposis
  • Spontaneous immortalization
  • Telomerase
  • Telomere

ASJC Scopus subject areas

  • Cancer Research

Cite this

Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient. / Forsyth, Nicholas R.; Morales, Carmela P.; Damle, Shirish; Boman, Bruce; Wright, Woodring E.; Kopelovich, Levy; Shay, Jerry W.

In: Neoplasia, Vol. 6, No. 3, 05.2004, p. 258-265.

Research output: Contribution to journalArticle

Forsyth, Nicholas R. ; Morales, Carmela P. ; Damle, Shirish ; Boman, Bruce ; Wright, Woodring E. ; Kopelovich, Levy ; Shay, Jerry W. / Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient. In: Neoplasia. 2004 ; Vol. 6, No. 3. pp. 258-265.
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