Re-expression of senescent markers in deinduced reversibly immortalized cells.

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.

journal_name

Exp Gerontol

journal_title

Experimental gerontology

authors

Shay JW,West MD,Wright WE

doi

10.1016/0531-5565(92)90003-i

keywords:

subject

Has Abstract

pub_date

1992-09-01 00:00:00

pages

477-92

issue

5-6

eissn

0531-5565

issn

1873-6815

journal_volume

27

pub_type

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