Genetic changes during immortalization of human cells

Spontaneous immortalization of fibroblasts containing an inherited mutation of one p53 allele was associated with loss of the wild-type p53 allele and loss of p16INK4 gene expression, but this combination of genetic events was insufficient for immortalization. Loss of p16INK4 expression appears to be an alternative to loss of functional retinoblastoma gene product. In all cell lines studied, immortalization was associated either with stabilization of telomere length in the presence of telomerase activity or with the acquisition of long and heterogeneous telomeres in the absence of detectable telomerase. The role of other genes, such as human stanniocalcin, in the immortalization process is under investigation. © 1995 Wiley-Liss, Inc.

[1]  E. Musgrove,et al.  Involvement of RB-1, p53, p16INK4 and telomerase in immortalisation of human cells. , 1995, Oncogene.

[2]  R. Reddel,et al.  Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts , 1995, Molecular and cellular biology.

[3]  R. Reddel,et al.  Telomere elongation in immortal human cells without detectable telomerase activity. , 1995, The EMBO journal.

[4]  D. Jong,et al.  A novel human cDNA highly homologous to the fish hormone stanniocalcin , 1995, Molecular and Cellular Endocrinology.

[5]  J. Bartek,et al.  Aberrations of p16Ink4 and retinoblastoma tumour‐suppressor genes occur in distinct sub‐sets of human cancer cell lines , 1995, International journal of cancer.

[6]  A. Okamoto,et al.  IS-12 Mutation and altered expression of P16^ in human cancer. , 1995 .

[7]  C. D. Edwards,et al.  Reciprocal Rb inactivation and p16INK4 expression in primary lung cancers and cell lines. , 1995, Cancer research.

[8]  G. Peters,et al.  Lack of cyclin D‐Cdk complexes in Rb‐negative cells correlates with high levels of p16INK4/MTS1 tumour suppressor gene product. , 1995, The EMBO journal.

[9]  O. Olopade,et al.  Increased p16 levels correlate with pRb alterations in human urothelial cells. , 1995, Cancer research.

[10]  C B Harley,et al.  Specific association of human telomerase activity with immortal cells and cancer. , 1994, Science.

[11]  A. Okamoto,et al.  Mutations and altered expression of p16INK4 in human cancer. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Reddel,et al.  HPV-16 E6 and E7 genes, like SV40 early region genes, are insufficient for immortalization of human mesothelial and bronchial epithelial cells. , 1994, Experimental cell research.

[13]  R. Reddel,et al.  In vitro transformation of Li-Fraumeni syndrome fibroblasts by SV40 large T antigen mutants. , 1994, Oncogene.

[14]  G. Hannon,et al.  A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 , 1993, Nature.

[15]  J. Shay,et al.  The frequency of immortalization of human fibroblasts and mammary epithelial cells transfected with SV40 large T-antigen. , 1993, Experimental cell research.

[16]  K. Keyomarsi,et al.  Differential display and cloning of messenger RNAs from human breast cancer versus mammary epithelial cells. , 1992, Cancer research.

[17]  R. Reddel,et al.  Germ-line splicing mutation of the p53 gene in a cancer-prone family. , 1992, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[18]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.

[19]  C. Harley,et al.  The telomere hypothesis of cellular aging , 1992, Experimental Gerontology.

[20]  J. Steitz,et al.  Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. , 1992, The EMBO journal.

[21]  C. Harley,et al.  Telomeres shorten during ageing of human fibroblasts , 1990, Nature.

[22]  J. R. Smith,et al.  Genetic analysis of indefinite division in human cells: identification of four complementation groups. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[23]  F. Jensen,et al.  SV40-INDUCED TRANFORMATION OF HUMAN DIPLOID CELLS: CRISIS AND RECOVERY. , 1965, Journal of cellular and comparative physiology.

[24]  L. Hayflick,et al.  The serial cultivation of human diploid cell strains. , 1961, Experimental cell research.

[25]  F. Kaye,et al.  Absence of p16INK4 protein is restricted to the subset of lung cancer lines that retains wildtype RB. , 1994, Oncogene.

[26]  R. Reddel,et al.  SV40-induced immortalization of human cells. , 1994, Critical reviews in oncogenesis.