Abstract
We have developed a simian virus 40 (SV40) T-antigen immortalized human cell line, 1MR90-D305.2H4 (IDH4), in which the expression of T-antigen is controlled by the mouse mammary tumor virus (MMTV) promoter and thus regulated by steroids such as dexamethasone. Studies on the regulation of proliferation by T-antigen led to the formulation of a two-stage model for human cell immortalization, in which a mortality stage 1 mechanism (M1) was the target of T-antigen action, and an independent mortality stage 2 mechanism (M2) produced crisis and prevented T-antigen from directly immortalizing cells. Rarely, a cell expressing T-antigen escaped crisis (e.g., M2) and was capable of indefinite proliferation. This model predicted that the deinduction of T-antigen in IDH4 cells would lead to the reexpression of the M1 mechanism, and thus a reexpression of the senescent phenotype. Our study confirms the prediction that, in the absence of steroids, IDH4 cells express a variety of morphological and biochemical markers characteristic of normal senescent human fibroblasts.
Original language | English (US) |
---|---|
Pages (from-to) | 477-492 |
Number of pages | 16 |
Journal | Experimental Gerontology |
Volume | 27 |
Issue number | 5-6 |
DOIs | |
State | Published - 1992 |
Keywords
- SV40 T-antigen
- cellular senescence
- reversible immortalization
ASJC Scopus subject areas
- Biochemistry
- Aging
- Molecular Biology
- Genetics
- Endocrinology
- Cell Biology