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Preferential primary-response gene expression in promotion-resistant versus promotion-sensitive JB6 cells
J L Cmarik1, H Herschman, N H Colburn
1Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Maryland 21702.
Molecular Carcinogenesis
|October 1, 1994
Summary
Tumor promotion involves specific 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequence (TIS) genes. TIS1 and TIS21 are preferentially induced in promotion-resistant cells, suggesting they may act as tumor promotion suppressor genes.
Area of Science:
- Molecular biology
- Cancer research
- Cell signaling
Background:
- 12-O-tetradecanoylphorbol-13-acetate (TPA)-inducible sequence (TIS) genes are primary response genes.
- TIS genes include transcription factors, prostaglandin synthase, and proteins of unknown function.
- Understanding TIS gene involvement in tumor promotion is crucial for cancer research.
Purpose of the Study:
- To investigate the role of TIS genes in tumor promotion.
- To examine TIS gene expression in transformation promotion-sensitive (P+) and -resistant (P-) JB6 murine epidermal cells.
- To identify TIS genes relevant to tumor promotion mechanisms.
Main Methods:
- Analyzed TIS gene expression in response to tumor promoters (TPA, epidermal growth factor) in P+ and P- JB6 cells.
- Quantified TIS mRNA and protein levels.
- Assessed the effects of anti-promoters (forskolin, fluocinolone acetonide, retinoic acid, superoxide dismutase) on TIS gene induction.
Main Results:
- TIS1, TIS10, and TIS21 were preferentially induced by TPA in P- cells.
- TIS1 and TIS21 mRNAs and proteins were upregulated in P- cells compared to P+ cells.
- Forskolin enhanced TPA-induced TIS1, TIS10, and TIS21 mRNA levels in P+ cells.
Conclusions:
- TIS1 and TIS21 are preferentially induced by tumor promoters in promotion-resistant cells.
- TIS1 and TIS21 show potential roles in modulating tumor promotion.
- TIS1 and TIS21 are candidates for promotion suppressor genes.