Heightened induction of c-jun mRNA by PMA, EGF and IL-1 in ataxia telangiectasia lymphoblasts.
OBJECTIVE
To determine if cells from the cancer-prone autosomal recessive disorder ataxia telangiectasia (A-T) are defective in responding to stimuli other than ionizing-radiation (IR) damage.


METHODS
The induction of c-jun transcripts by IR, by phorbol 12-myristate 13-acetate (PMA), interleukin 1 (IL-1) and epidermal growth factor (EGF) in normal and A-T lymphoblasts was measured.


RESULTS
Treatment with PMA increased c-jun transcripts in a dose- and time-dependent manner two- to three-fold more in A-T than in normal cells. Similarly, treatment with EGF and IL-1 also increased c-jun transcripts more in A-T than in normal lymphoblasts. In contrast, exposure to gamma-radiation increased c-jun transcripts at least twofold more in normal than in A-T lymphoblasts.


CONCLUSIONS
These findings indicate that A-T cells are not only defective in responding to IR damage, but also in responding to mitogenic stimuli like IL-1 and EGF. Furthermore, these findings implicate ATM, the gene responsible for the A-T disorder, in the induction of c-jun transcripts by PMA, EGF or IL-1.
Sikpi
M O
MO
Department of Oral Diagnosis, School of Dental Medicine, University of Connecticut Health Center, Farmington 06030, USA. sikpi@nso2.uchc.edu
Wang
Y
Y
Mallya
S M
SM
D001260:Ataxia Telangiectasia / Q000235:genetics* / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D016758:Genes, jun; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism* / Q000528:radiation effects; D008934:Mitogens / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D011836:Radiation Tolerance; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D007375:Interleukin-1; D008934:Mitogens; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D004815:Epidermal Growth Factor; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D013755:Tetradecanoylphorbol Acetate