PMID- 8843413
OWN - NLM
STAT- MEDLINE
DCOM- 19970408
LR  - 20220408
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 10
IP  - 8
DP  - 1996 Aug
TI  - Transcriptional control of steroid-regulated apoptosis in murine thymoma cells.
PG  - 967-78
AB  - Early studies in murine T cell lines indicated that transcriptional 
      transactivation functions encoded in the glucocorticoid receptor (GR) N-terminal 
      domain are required for glucocorticoid-mediated apoptosis. However, more recent 
      studies in human T cell lines have suggested that the N-terminal domain is not 
      necessary for steroid-regulated apoptosis and that GR-mediated transrepression 
      may be the more critical mechanism. To better understand the contribution of the 
      GR N-terminal transactivation domain in mediating murine thymocyte apoptosis, we 
      stably transfected GR, GR variants, and the androgen receptor (AR) into 
      receptor-negative S49 murine thymoma cells. GR expression levels were shown to be 
      rate-limiting for initiating the apoptotic pathway, and a positive correlation 
      between steroid sensitivity and GR-mediated induction of an integrated mouse 
      mammary tumor virus (MMTV) LTR reporter gene was observed. Analysis of GR 
      chimeric receptors containing the potent VP16 and E1A viral transactivation 
      domains in place of the GR N terminus revealed that even low level expression of 
      these receptors resulted in both enhanced steroid sensitivity and MMTV induction, 
      thus supporting a role for transactivation in apoptosis. In contrast, we found 
      that AR can initiate apoptosis in S49 cells after treatment with 5 
      alpha-dihydrotestosterone, despite its relative inability to induce high level 
      expression of MMTV. To investigate this further, we examined the 
      steroid-regulated expression of an endogenous thymocyte-specific gene called 
      GIG18. We found that GIG18 was rapidly induced to comparable levels by both AR 
      and GR, demonstrating that AR can indeed function as a transcriptional activator 
      in S49 cells and, moreover, that GIG18 induction may be a marker of early 
      apoptotic events in steroid-treated cells. Taken together, these results support 
      our conclusion that transcriptional transactivation is a necessary signaling 
      component of S49 cell apoptosis, although an additional role for GR-mediated 
      transrepression cannot be excluded.
FAU - Chapman, M S
AU  - Chapman MS
AD  - Department of Biochemistry, University of Arizona, Tucson 85721, USA.
FAU - Askew, D J
AU  - Askew DJ
FAU - Kuscuoglu, U
AU  - Kuscuoglu U
FAU - Miesfeld, R L
AU  - Miesfeld RL
LA  - eng
GR  - GM-40738/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Receptors, Androgen)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Dexamethasone/*pharmacology
MH  - Dihydrotestosterone/pharmacology
MH  - Genes, Reporter
MH  - Humans
MH  - Mammary Tumor Virus, Mouse/genetics
MH  - Mice
MH  - Receptors, Androgen/genetics/physiology
MH  - Receptors, Glucocorticoid/genetics/physiology
MH  - T-Lymphocytes
MH  - Thymoma/*pathology
MH  - Thymus Neoplasms/*pathology
MH  - *Transcription, Genetic
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1996/08/01 00:00
MHDA- 1996/08/01 00:01
CRDT- 1996/08/01 00:00
PHST- 1996/08/01 00:00 [pubmed]
PHST- 1996/08/01 00:01 [medline]
PHST- 1996/08/01 00:00 [entrez]
AID - 10.1210/mend.10.8.8843413 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1996 Aug;10(8):967-78. doi: 10.1210/mend.10.8.8843413.