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Real-time in vivo imaging of p16gene expression: a new approach to study senescence stress signaling in living animals.

Ohtani N, Yamakoshi K, Takahashi A, Hara E - Cell Div (2010)

Bottom Line: To date, much of our current knowledge of how human p16(INK4a )gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells.However, since human p16(INK4a )gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16(INK4a )gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress.Here, we discuss the molecular mechanisms that direct p16(INK4a )gene expression in vivo and its potential for tumor suppression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cancer Biology, Cancer Institute, Japanese Foundation for Cancer Research (JFCR), 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

ABSTRACT
Oncogenic proliferative signals are coupled to a variety of growth inhibitory processes. In cultured primary human fibroblasts, for example, ectopic expression of oncogenic Ras or its downstream mediator initiates cellular senescence, the state of irreversible cell cycle arrest, through up-regulation of cyclin-dependent kinase (CDK) inhibitors, such as p16(INK4a). To date, much of our current knowledge of how human p16(INK4a )gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells. However, since human p16(INK4a )gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16(INK4a )gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress. To eliminate any potential problems arising from tissue culture imposed stress, we have recently developed a bioluminescence imaging (BLI) system for non-invasive and real-time analysis of human p16(INK4a )gene expression in the context of a living animal. Here, we discuss the molecular mechanisms that direct p16(INK4a )gene expression in vivo and its potential for tumor suppression.

No MeSH data available.


Related in: MedlinePlus

Real-time bioluminescence imaging of p16INK4a gene expression during aging process in vivo. The same p16-luc mice were subjected to noninvasive BLI throughout their entire life span. The level of bioluminescent signals is significantly increased throughout the body during aging.
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Figure 2: Real-time bioluminescence imaging of p16INK4a gene expression during aging process in vivo. The same p16-luc mice were subjected to noninvasive BLI throughout their entire life span. The level of bioluminescent signals is significantly increased throughout the body during aging.

Mentions: By monitoring and quantifying the bioluminescent signal repeatedly in the same p16-luc mouse throughout its entire lifespan, we were able to unveil the dynamics of human p16INK4a gene expression in the aging process of the transgenic mouse (Figure 2). Importantly moreover, the bioluminescence signal levels correlated well with not only exogenous (human) but also endogenous (mouse) p16INK4a gene expression, indicating that overall regulation of human p16INK4a gene expression is very similar to that of mouse p16INK4a gene expression, at least in mouse cells[37]. This is consistent with the previous notion that the levels of p16INK4a gene expression were increased during the aging process of both rodents and primates [20,40-43]. These results illustrate the potential of the p16-luc mice for the analysis of p16INK4a gene expression in response to oncogenic stimuli in vivo.


Real-time in vivo imaging of p16gene expression: a new approach to study senescence stress signaling in living animals.

Ohtani N, Yamakoshi K, Takahashi A, Hara E - Cell Div (2010)

Real-time bioluminescence imaging of p16INK4a gene expression during aging process in vivo. The same p16-luc mice were subjected to noninvasive BLI throughout their entire life span. The level of bioluminescent signals is significantly increased throughout the body during aging.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2821322&req=5

Figure 2: Real-time bioluminescence imaging of p16INK4a gene expression during aging process in vivo. The same p16-luc mice were subjected to noninvasive BLI throughout their entire life span. The level of bioluminescent signals is significantly increased throughout the body during aging.
Mentions: By monitoring and quantifying the bioluminescent signal repeatedly in the same p16-luc mouse throughout its entire lifespan, we were able to unveil the dynamics of human p16INK4a gene expression in the aging process of the transgenic mouse (Figure 2). Importantly moreover, the bioluminescence signal levels correlated well with not only exogenous (human) but also endogenous (mouse) p16INK4a gene expression, indicating that overall regulation of human p16INK4a gene expression is very similar to that of mouse p16INK4a gene expression, at least in mouse cells[37]. This is consistent with the previous notion that the levels of p16INK4a gene expression were increased during the aging process of both rodents and primates [20,40-43]. These results illustrate the potential of the p16-luc mice for the analysis of p16INK4a gene expression in response to oncogenic stimuli in vivo.

Bottom Line: To date, much of our current knowledge of how human p16(INK4a )gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells.However, since human p16(INK4a )gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16(INK4a )gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress.Here, we discuss the molecular mechanisms that direct p16(INK4a )gene expression in vivo and its potential for tumor suppression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cancer Biology, Cancer Institute, Japanese Foundation for Cancer Research (JFCR), 3-8-31, Ariake, Koto-ku, Tokyo, 135-8550, Japan.

ABSTRACT
Oncogenic proliferative signals are coupled to a variety of growth inhibitory processes. In cultured primary human fibroblasts, for example, ectopic expression of oncogenic Ras or its downstream mediator initiates cellular senescence, the state of irreversible cell cycle arrest, through up-regulation of cyclin-dependent kinase (CDK) inhibitors, such as p16(INK4a). To date, much of our current knowledge of how human p16(INK4a )gene expression is induced by oncogenic stimuli derives from studies undertaken in cultured primary cells. However, since human p16(INK4a )gene expression is also induced by tissue culture-imposed stress, it remains unclear whether the induction of human p16(INK4a )gene expression in tissue-cultured cells truly reflects an anti-cancer process or is an artifact of tissue culture-imposed stress. To eliminate any potential problems arising from tissue culture imposed stress, we have recently developed a bioluminescence imaging (BLI) system for non-invasive and real-time analysis of human p16(INK4a )gene expression in the context of a living animal. Here, we discuss the molecular mechanisms that direct p16(INK4a )gene expression in vivo and its potential for tumor suppression.

No MeSH data available.


Related in: MedlinePlus