Identification of RHOXF2 (PEPP2) as a cancer-promoting gene by expression cloning

Abstract

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.

Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies

“…On the other hand, PEPP2 expression in PBMNC or BMMNC from healthy donors was not observed or was extremely low compared to leukemia cells, which suggests that PEPP2 is an ideal target for therapy of leukemia. We didn’t observe high expression of the PEPP2 gene in other types of cancer cells including brain tumor, lung cancer, and pancreatic cancer, although it has been reported that this gene is expressed in colon cancer and gastric cancer [ 26 ], which were not included in our sample set.…”

“…Li et al [ 25 ] showed that knockdown of Rhox5 in a colon cancer cell line suppressed cell proliferation and migration in mice. There is also a report that transducion of PEPP2 into murine monocytic leukemia cell line enhanced leukemogenesis in irradiated mice [ 26 ]. These results indicate an important role of PEPP2 in the development of leukemia and suggest that targeting PEPP2 might be effective in the eradication of leukemia cells.…”

<p>LOXL1-AS1 Contributes to Non-Small Cell Lung Cancer Progression by Regulating miR-3128/RHOXF2 Axis</p>

“…In a previous study, RHOXF2 has been confirmed to be higher expressed in various cancer cell lines, such as lung cancer, colon cancer and leukemia cell lines. 26 In breast cancer patients, it was considered as a recognized biomarker at the transcript level. 27 Compared with normal tissue, the expression of RHOXF2 in breast cancer was upregulated by 3.31 fold in breast cancerous tissues.…”

Genetic and molecular biology of breast cancer among Iranian patients

“…ODF is involved in sperm tail maintenance and centrosome matrix [269] which facilitates the tumor cell proliferation. The RHOXF2 is associated with cell transformation [270] and cell to cell contacts [271]. The ODF4 and RHOXF2 cancer testis antigens had overexpression in tumors compared with normal marines in a sub population of Iranian BC patients [272].…”