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Inhibitory effect of ATF3 antisense oligonucleotide on ectopic growth of HT29 human colon cancer cells
T Ishiguro1, H Nagawa, M Naito
1Department of Surgical Oncology, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Abstract:
ATF3 is a transcription factor belonging to the Jun / Fos family whose mouse homologue (TI-241) was isolated, using the differential screening method, from B16 mouse melanoma cells as a blood-borne metastasis-associated gene. Here we show the tumorigenicity-inhibiting effect of an antisense oligonucleotide designed to reduce the expression of ATF3 in HT29 colon cancer cells. HT29 cells were reported to metastasize to the skin after intravenous inoculation. The antisense oligonucleotide inhibited cell attachment to the collagen-coated floor of the plates and invasion of HT29 cells in vitro, which are thought to be two important factors in the process of cancer metastasis and ectopic tumor growth. While the antisense oligonucleotide had no effect on cell growth of HT29 cells in vitro, mice that were inoculated subcutaneously with HT29 cells and treated with the antisense oligonucleotide survived longer than the control mice due to the inhibition of tumor growth in vivo. These show that ATF3 plays an important role in the ectopic growth / metastasis of HT29 colon cancer cells.
Insights
Reducing activating transcription factor 3 (ATF3) expression with antisense oligonucleotides inhibited colon cancer cell metastasis and growth. This strategy prolonged survival in mice, highlighting ATF3
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Activating transcription factor 3 (ATF3) is a Jun/Fos family transcription factor.
- Its mouse homologue (TI-241) was identified as a metastasis-associated gene in melanoma cells.
- ATF3's role in colon cancer metastasis was not well understood.
Purpose of the Study:
- To investigate the role of ATF3 in HT29 colon cancer cell metastasis.
- To evaluate the therapeutic potential of inhibiting ATF3 expression using antisense oligonucleotides.
Main Methods:
- HT29 colon cancer cells were treated with an ATF3-targeting antisense oligonucleotide.
- In vitro assays assessed cell attachment to collagen and cell invasion.
- In vivo studies involved subcutaneous inoculation of HT29 cells in mice, followed by antisense oligonucleotide treatment.
Main Results:
- The antisense oligonucleotide significantly inhibited HT29 cell attachment and invasion in vitro.
- Inhibition of ATF3 expression did not affect HT29 cell growth in vitro.
- Mice treated with the antisense oligonucleotide exhibited reduced tumor growth and increased survival rates compared to controls.
Conclusions:
- ATF3 plays a critical role in the ectopic growth and metastasis of HT29 colon cancer cells.
- Targeting ATF3 with antisense oligonucleotides demonstrates a promising strategy for inhibiting colon cancer metastasis and progression.
- This study provides evidence for ATF3 as a potential therapeutic target in colon cancer treatment.
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