Dose-dependent induction of resistance to terminal differentiation in x-irradiated cultures of normal human keratinocytes.

Tuynder, Marcel; Godfrine, S.; Cornelis, Jan J.; Rommelaere, Jean

doi:10.1073/pnas.88.7.2638

Cited by 11 publications

(8 citation statements)

References 23 publications

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“…The simian virus 40-transformed newborn human kidney cell line NB-E (45), its derivative NB324K, and A9, a subline of mouse L cells (29), were grown in minimal essential medium (GIBCO), as were the human cervical carcinoma cell line HeLa, the spontaneously immortalized human keratinocytes HaCat (4), the simian virus 40-trans-formed human lung fibroblast line MRC5-V1 (26), the y-6'Cotransformed human fibroblast line KMST6 (33), and NHF-5, a normal, finite-life human foreskin fibroblast strain derived from a primary culture (infected at passage 4 or 5). Normal nondifferentiated human keratinocytes (NHK) were isolated from neonatal foreskins by the method of Tuynder et al (53). NHK cells were grown in (serum-free) keratinocyte-SFM medium (GIBCO) and infected at passages 1 or 2.…”

Section: Methodsmentioning

confidence: 99%

Use of an autonomous parvovirus vector for selective transfer of a foreign gene into transformed human cells of different tissue origins and its expression therein

Dupont

Tenenbaum

Guo

et al. 1994

J Virol

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In this work, we report the transduction of a chloramphenicol acetyltransferase (CAT) reporter gene into a variety of normal and transformed human cells of various tissue origins. The vector used was MVM/P38cat, a recombinant of the prototype strain of the autonomous parvovirus minute virus of mice (MVMp). The CAT gene was inserted into the capsid-encoding region of the infectious molecular clone of MVMp genome, under the control of the MVM P38 promoter. When used to transfect permissive cells, the MVM/P38cat DNA was efficiently replicated and expressed the foreign CAT gene at high levels. By cotransfecting with a helper plasmid expressing the capsid proteins, it was possible to produce mixed virus stocks containing MVM/P38cat infectious particles and variable amounts of recombinant MVM. MVM/P38cat viral particles were successfully used to transfer the CAT gene and to express it in a variety of human cells. Both viral DNA replication and P38-driven CAT expression were achieved in fibroblasts, epithelial cells, T lymphocytes, and macrophages in a transformation-dependent way, but with an efficiency depending on the cell type. In transformed B

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Section: Methodsmentioning

confidence: 99%

Use of an autonomous parvovirus vector for selective transfer of a foreign gene into transformed human cells of different tissue origins and its expression therein

Dupont

Tenenbaum

Guo

et al. 1994

J Virol

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“…In the first study, radiation-transformed human fibroblasts formed foci in vitro and formed tumors in nude mice (14); in the second study, fibroblasts became immortal and underwent further spontaneous transformation after continuous culture (35,36). The third study reported that radiationtreated keratinocytes became immortal but not tumorigenic (42). Thus, 76R-30, together with its normal parent cell strain (76N), represents the first model of radiation-induced tumorigenic transformation of human mammary epithelial cells.…”

Section: S L 18smentioning

confidence: 99%

“…The (8,15). The status of p53 protein in other radiation-transformed human cells established by others has not been reported (14,36,42). However, a high incidence of p53 mutations has been observed in murine UV-and y-irradiation-induced tumors (26,30).…”

Section: S L 18smentioning

confidence: 99%

“…Further analysis showed that 76R-30 cells could grow as tumors in nude mice, establishing directly that these cells had undergone tumorigenic transformation as a consequence of irradiation. To our knowledge, there are only three reports of radiation transformation of primary human cells, two with fibroblasts (14, 36) and one using keratinocytes (42). In the first study, radiation-transformed human fibroblasts formed foci in vitro and formed tumors in nude mice (14); in the second study, fibroblasts became immortal and underwent further spontaneous transformation after continuous culture (35,36).…”

Section: S L 18smentioning

confidence: 99%

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Loss of p53 protein during radiation transformation of primary human mammary epithelial cells.

Wazer¹,

Chu²,

Liu³

et al. 1994

Mol. Cell. Biol.

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The causative factors leading to breast cancer are largely unknown. Increased incidence of breast cancer following diagnostic or therapeutic radiation suggests that radiation may contribute to mammary oncogenesis. This report describes the in vitro neoplastic transformation of a normal human mammary epithelial cell strain, 76N, by fractionated gamma-irradiation at a clinically used dose (30 Gy). The transformed cells (76R-30) were immortal, had reduced growth factor requirements, and produced tumors in nude mice. Remarkably, the 76R-30 cells completely lacked the p53 tumor suppressor protein. Loss of p53 was due to deletion of the gene on one allele and a 26-bp deletion within the third intron on the second allele which resulted in abnormal splicing out of either the third or fourth exon from the mRNA. PCR with a mutation-specific primer showed that intron 3 mutation was present in irradiated cells before selection for immortal phenotype. 76R-30 cells did not exhibit G1 arrest in response to radiation, indicating a loss of p53-mediated function. Expression of the wild-type p53 gene in 76R-30 cells led to their growth inhibition. Thus, loss of p53 protein appears to have contributed to neoplastic transformation of these cells. This unique model should facilitate analyses of molecular mechanisms of radiation-induced breast cancer and allow identification of p53-regulated cellular genes in breast cells.

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“…Recently, a few immortal human cell lines have been established from normal human cells in culture following repeated exposure to radiation or chemical mutagens. These include cell lines derived from diploid fibroblasts (14,15), mammary epithelial cells (25), and keratinocytes (29). In an attempt to identify a senescence or mortality gene(s) involved in normal diploid fibroblasts, we used two of these nontumorgenic immortalized human cell lines, KMST-6 (KMST) and SUSM-1 (SUSM), which were established from fetal human fibroblasts after repeated gamma irradiation and 4-NQO treatment, respectively (14,15).…”

mentioning

confidence: 99%

Chromosome 7 suppresses indefinite division of nontumorigenic immortalized human fibroblast cell lines KMST-6 and SUSM-1.

Ogata¹,

Ayusawa²,

Namba³

et al. 1993

Mol. Cell. Biol.

104

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Using nontumorigenic immortalized human cell lines KMST-6 (KMST) and SUSM-1 (SUSM), we attempted to identify the chromosome that carries a putative senescence-related gene(s). These cell lines are the only ones that have been established independently from normal human diploid fibroblasts following in vitro mutagenesis. We first examined restriction fragment length polymorphisms on each chromosome of these immortalized cell lines and their parental cell lines and found specific chromosomal alterations common to these cell lines (a loss of heterozygosity in KMST and a deletion in SUSM) on the long arm of chromosome 7. In addition to these, we also found that introduction of chromosome 7 into these cell lines by means of microcell fusion resulted in the cessation of cell division, giving rise to cells resembling cells in senescence. Introduction of other chromosomes, such as chromosomes 1 and 11, on which losses of heterozygosity were also detected in one of the cell lines (KMST), to either KMST or SUSM cells or of chromosome 7 to several tumor-derived cell lines had no effect on their division potential. These results strongly suggest that a gene(s) affecting limited-division potential or senescence of normal human fibroblasts is located on chromosome 7, probably at the long arm of the chromosome, representing the first case in which a specific chromosome reverses the immortal phenotype of otherwise normal human cell lines.

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Dose-dependent induction of resistance to terminal differentiation in x-irradiated cultures of normal human keratinocytes.

Cited by 11 publications

References 23 publications

Use of an autonomous parvovirus vector for selective transfer of a foreign gene into transformed human cells of different tissue origins and its expression therein

Use of an autonomous parvovirus vector for selective transfer of a foreign gene into transformed human cells of different tissue origins and its expression therein

Loss of p53 protein during radiation transformation of primary human mammary epithelial cells.

Chromosome 7 suppresses indefinite division of nontumorigenic immortalized human fibroblast cell lines KMST-6 and SUSM-1.

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