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A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

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Fusion produces transformed hybrids from cells destined to die. (A) Detroit 551 cells freshly transduced with E1A and resistant to hygromycin (DEH), transduced with Ha-Ras and resistant to puromycin (DRasP), or cotransduced with both E1A and Ha-Ras and resistant to both antibiotics (DE1ARasHP) were cultured for 16 h alone or in combination, as indicated, with or without MPMVE. The cells were then cultured for 7 d without added virus in medium containing hygromycin (DEH), puromycin (DRasP), or both (DE1ARasHP and the co-cultured DEH and DRasP treated with MPMVE). The cells were then collected, plated into soft agar at equal cell densities as indicated, cultured for 20 d, and visualized by crystal violet. (B) Cell colonies in the corresponding bottom panels in A. The experiment was done four times with similar results. Bars, 100 μm.
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fig8: Fusion produces transformed hybrids from cells destined to die. (A) Detroit 551 cells freshly transduced with E1A and resistant to hygromycin (DEH), transduced with Ha-Ras and resistant to puromycin (DRasP), or cotransduced with both E1A and Ha-Ras and resistant to both antibiotics (DE1ARasHP) were cultured for 16 h alone or in combination, as indicated, with or without MPMVE. The cells were then cultured for 7 d without added virus in medium containing hygromycin (DEH), puromycin (DRasP), or both (DE1ARasHP and the co-cultured DEH and DRasP treated with MPMVE). The cells were then collected, plated into soft agar at equal cell densities as indicated, cultured for 20 d, and visualized by crystal violet. (B) Cell colonies in the corresponding bottom panels in A. The experiment was done four times with similar results. Bars, 100 μm.

Mentions: Cell fusion can add to cell diversity by combining distinct properties of the fusion partners. For example, genes that are insufficient to transform on their own may be brought together by cell fusion to result in a transforming combination. To test whether MPMVE has this effect, we used the observation that expressing E1A together with oncogenic Ras results in transformed cells that grow in soft agar, whereas expressing E1A alone induces apoptosis and expressing Ras senescence (Seger et al., 2002). Indeed, Detroit 511 cells that were freshly transduced with E1A (DEH) or that expressed Ha-Ras (DRasP) alone failed to form colonies in soft agar (Fig. 8). In contrast, hybrids of DEH and DRasP produced by MPMVE grew at least as efficiently in soft agar as did the cells cotransduced with E1A and Ha-Ras (Fig. 5). Hybrids recovered from soft agar also grew efficiently in tissue culture, whereas no parental cells could be recovered, implying that neighboring cells, even if they are otherwise destined to die, could produce transformed proliferating progeny if fused by a virus.


A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Fusion produces transformed hybrids from cells destined to die. (A) Detroit 551 cells freshly transduced with E1A and resistant to hygromycin (DEH), transduced with Ha-Ras and resistant to puromycin (DRasP), or cotransduced with both E1A and Ha-Ras and resistant to both antibiotics (DE1ARasHP) were cultured for 16 h alone or in combination, as indicated, with or without MPMVE. The cells were then cultured for 7 d without added virus in medium containing hygromycin (DEH), puromycin (DRasP), or both (DE1ARasHP and the co-cultured DEH and DRasP treated with MPMVE). The cells were then collected, plated into soft agar at equal cell densities as indicated, cultured for 20 d, and visualized by crystal violet. (B) Cell colonies in the corresponding bottom panels in A. The experiment was done four times with similar results. Bars, 100 μm.
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Related In: Results  -  Collection

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fig8: Fusion produces transformed hybrids from cells destined to die. (A) Detroit 551 cells freshly transduced with E1A and resistant to hygromycin (DEH), transduced with Ha-Ras and resistant to puromycin (DRasP), or cotransduced with both E1A and Ha-Ras and resistant to both antibiotics (DE1ARasHP) were cultured for 16 h alone or in combination, as indicated, with or without MPMVE. The cells were then cultured for 7 d without added virus in medium containing hygromycin (DEH), puromycin (DRasP), or both (DE1ARasHP and the co-cultured DEH and DRasP treated with MPMVE). The cells were then collected, plated into soft agar at equal cell densities as indicated, cultured for 20 d, and visualized by crystal violet. (B) Cell colonies in the corresponding bottom panels in A. The experiment was done four times with similar results. Bars, 100 μm.
Mentions: Cell fusion can add to cell diversity by combining distinct properties of the fusion partners. For example, genes that are insufficient to transform on their own may be brought together by cell fusion to result in a transforming combination. To test whether MPMVE has this effect, we used the observation that expressing E1A together with oncogenic Ras results in transformed cells that grow in soft agar, whereas expressing E1A alone induces apoptosis and expressing Ras senescence (Seger et al., 2002). Indeed, Detroit 511 cells that were freshly transduced with E1A (DEH) or that expressed Ha-Ras (DRasP) alone failed to form colonies in soft agar (Fig. 8). In contrast, hybrids of DEH and DRasP produced by MPMVE grew at least as efficiently in soft agar as did the cells cotransduced with E1A and Ha-Ras (Fig. 5). Hybrids recovered from soft agar also grew efficiently in tissue culture, whereas no parental cells could be recovered, implying that neighboring cells, even if they are otherwise destined to die, could produce transformed proliferating progeny if fused by a virus.

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

Show MeSH
Related in: MedlinePlus