Related Experiment Videos
Amphiregulin is a vitamin D3 target gene in squamous cell and breast carcinoma
Abstract:
1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)2D3] inhibits growth of cells derived from a variety of tumors in vitro and in vivo. Proliferation in vitro of human SCC25 cells, derived from a primary squamous cell carcinoma (SCC) of the tongue, was blocked by 1,25(OH)2D3 and its analog EB1089. A similar effect was observed with 13-cis retinoic acid (RA), which has been used in chemoprevention of SCC. We identified amphiregulin, a member of the epidermal growth factor family, as a 1,25(OH)2D3 target gene in SCC25 cells. Induction of amphiregulin mRNA by 1,25(OH)2D3 was rapid and sustained over 48 h, and was unaffected by cycloheximide. 1,25(OH)2D3 also induced amphiregulin mRNA in estrogen receptor-positive and -negative human breast cancer cell lines, but not in LNCaP human prostate cancer cells. RAR- or RXR-specific retinoids did not affect amphiregulin mRNA levels in SCC25 cells; however, 13-cis RA partially blocked the response to 1,25(OH)2D3. Amphiregulin partially inhibited growth of SCC25 cells in culture. Our data show that amphiregulin is a 1,25(OH)2D3 target gene, and suggest that its induction may contribute to the growth inhibitory effects of 1,25(OH)2D3.
Insights
1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)2D3] and retinoids inhibit squamous cell carcinoma (SCC) growth. Researchers found 1,25(OH)2D3 targets amphiregulin, a gene that may mediate its anti-cancer effects.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- 1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)2D3] demonstrates anti-proliferative effects against various cancer cells in vitro and in vivo.
- Squamous cell carcinoma (SCC) is a common cancer, and chemoprevention strategies are actively sought.
- Retinoids, such as 13-cis retinoic acid (RA), are used in SCC chemoprevention.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the growth inhibitory effects of 1,25(OH)2D3 in SCC.
- To identify specific genes regulated by 1,25(OH)2D3 in SCC cells.
- To explore the role of amphiregulin in 1,25(OH)2D3-mediated growth inhibition.
Main Methods:
- Cell culture of human SCC25 cells (tongue SCC) and human breast cancer cell lines.
- Treatment with 1,25(OH)2D3, its analog EB1089, and 13-cis retinoic acid (RA).
- Quantitative analysis of amphiregulin mRNA expression using RT-PCR; assessment of cell proliferation.
Main Results:
- 1,25(OH)2D3 and EB1089 significantly inhibited proliferation of SCC25 cells.
- Amphiregulin was identified as a 1,25(OH)2D3 target gene, with its mRNA induction being rapid and sustained.
- 1,25(OH)2D3 also induced amphiregulin in breast cancer cells but not prostate cancer cells.
- 13-cis RA partially blocked the 1,25(OH)2D3-induced response, while RAR/RXR-specific retinoids had no effect.
- Amphiregulin itself partially inhibited SCC25 cell growth.
Conclusions:
- Amphiregulin is a direct 1,25(OH)2D3 target gene in SCC cells.
- The induction of amphiregulin may contribute to the observed growth inhibitory effects of 1,25(OH)2D3 in SCC.
- These findings provide insights into the molecular pathways targeted by vitamin D analogs in cancer therapy.