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[Antisense TIF3 reverses the oncogenic potential of CdCl2-transformed BALB/c-3T3 cells]
Yixiong Lei1, Joseph Pius, Zhongliang Wu
1Institute for Chemical Carcinogenesis, Guangzhou Medical College, Guangzhou 510182, China.
Abstract:
TIF3 (GenBank Accession Number AF 271072) is identified as a novel cadmium- responsive proto-oncogene. In order to determine whether the antisense TIF3 reverses the oncogenic potential of Cd-transformed BALB/c-3T3 cells or not, a stable expression system of CdCl2-transformed BALB/c-3T3 cells with the expression vector containing TIF3 cDNA in the antisense orientation using calcium phosphate and G418 selection protocols is firstly established. Then, the reversal of the oncogenic potential of these cells is tested by soft agar and nude mouse tumorigenicity assay. The results demonstrated that expression of the antisense TIF3 in the CdCl2-transformed BALB/c-3T3 cells results in reversal of the transformed phenotype of the cells. This is evidenced by a 25%-70% decrease in the number of anchorage-independent colonies growing on soft agar and the significant reduced tumorigenic potential of cells in nude mice compared with the corresponding controls. In addition to a significant delay in the onset of appearance of tumors, a significant reduction in size and a 50.8%-55.1% decrease in weight of the tumors are also observed in the mice injected with the TIF3 antisense expressing cells compared with the corresponding controls. The results indicate that antisense TIF3 mRNA expression reverses its oncogenic potential of Cd-transformed BALB/c-3T3 cells and may have therapeutic potential to cancer induced by cadmium.
Insights
Antisense TIF3 expression reversed the oncogenic potential of cadmium-transformed cells, reducing tumor formation and growth in mice. This suggests therapeutic potential for cadmium-induced cancers.
Area of Science:
- Molecular Biology
- Oncology
- Toxicology
Context:
- Cadmium (Cd) exposure is linked to cancer development.
- TIF3 is identified as a novel cadmium-responsive proto-oncogene.
- Understanding TIF3's role in cadmium-induced carcinogenesis is crucial.
Purpose:
- To investigate if antisense TIF3 can reverse the oncogenic potential of Cd-transformed BALB/c-3T3 cells.
- To establish a stable expression system for antisense TIF3 in Cd-transformed cells.
- To evaluate the therapeutic potential of antisense TIF3 in cadmium-induced cancer.
Summary:
- A stable expression system for antisense TIF3 was established in cadmium chloride (CdCl2)-transformed BALB/c-3T3 cells.
- Antisense TIF3 expression significantly reduced anchorage-independent colony formation in soft agar (25%-70% decrease).
- Tumorigenicity assays in nude mice showed reduced tumor onset, size, and weight (50.8%-55.1% decrease) in mice injected with TIF3 antisense-expressing cells.
Impact:
- Antisense TIF3 expression reverses the transformed phenotype of Cd-transformed cells.
- This study highlights the potential of antisense TIF3 as a therapeutic agent for cadmium-induced cancers.
- Findings contribute to understanding cadmium's oncogenic mechanisms and developing targeted cancer therapies.