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Identification of RHOXF2 (PEPP2) as a cancer-promoting gene by expression cloning
Fumi Shibata-Minoshima1, Toshihiko Oki, Noriko Doki
1Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Abstract:
Multiple mutations contribute to establish cancers. We have searched for potential oncogenes by screening cDNA libraries derived from gastric cancer cell lines, pancreatic cancer cell lines and glioma cell lines, using retrovirus-mediated expression cloning. Two types of interleukin-3 (IL-3)-dependent cell lines, Ba/F3 and HF6, were transduced with the cDNA libraries and several genes that render these cells factor-independent were identified including PIM-1, PIM-2, PIM-3, GADD45B and reproductive homeobox genes on the X chromosome gene F2 (RHOXF2). Although no mutation in these genes was found, these molecules were highly expressed in cancer cell lines and they may play important roles in cell transformation. Among them, we focused on a transcriptional repressor RHOXF2. Transduction of RHOXF2 rendered HF6 cells factor-independent, while knockdown of RHOXF2 inhibited growth of the HGC27 gastric cancer cell line which highly expresses RHOXF2. In addition, RHOXF2-transduced HF6 cells quickly induced leukemia when transplanted into sublethally irradiated mice. Moreover, RHOXF2 is highly expressed in some leukemia cell lines and a variety of human cancer samples including colon and lung cancers. Thus, these results indicate that RHOXF2 is involved in carcinogenesis.
Insights
Researchers identified RHOXF2 as a potential oncogene driving cancer development. This gene promotes cell transformation and factor independence, indicating its role in carcinogenesis and potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Gene Expression
Background:
- Cancer arises from multiple genetic mutations.
- Identifying novel oncogenes is crucial for understanding cancer development.
Purpose of the Study:
- To screen for potential oncogenes involved in cancer.
- To investigate the role of RHOXF2 in cell transformation and carcinogenesis.
Main Methods:
- Retrovirus-mediated expression cloning using cDNA libraries from gastric, pancreatic, and glioma cancer cell lines.
- Transduction of interleukin-3 (IL-3)-dependent cell lines (Ba/F3, HF6) with identified genes.
- Knockdown experiments in gastric cancer cell line (HGC27).
- In vivo studies involving transplantation into mice.
Main Results:
- Identified several genes, including RHOXF2, that confer factor independence to IL-3-dependent cells.
- RHOXF2 expression was high in cancer cell lines and promoted factor independence in HF6 cells.
- Knockdown of RHOXF2 inhibited growth of RHOXF2-expressing gastric cancer cells.
- RHOXF2-expressing cells induced leukemia in mice, and RHOXF2 is highly expressed in various human cancers.
Conclusions:
- RHOXF2 acts as a transcriptional repressor and oncogene.
- RHOXF2 plays a significant role in cell transformation and carcinogenesis.
- RHOXF2 is a potential therapeutic target for various cancers.
