Tumor promoting properties of the ETS protein MEF in ovarian cancer

Abstract

We have previously shown that MEF (myeloid ELF1-like factor, also known as ELF4) functions as a transcriptional activator of the interleukin (IL)-8, perforin, granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-3 genes in hematopoietic cells. MEF is also expressed in non-hematopoietic tissues including certain ovarian cancer cells. To define the function of MEF in these cells, we examined primary human ovarian epithelial tumors and found that MEF is expressed in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3 ovarian cancer cell lines, but not in normal ovarian surface epithelium. Manipulating MEF levels in these cell lines altered their behavior; reducing MEF levels, using short hairpin RNA expressing vectors, significantly inhibited the proliferation of SKOV3 and CAOV3 cells in culture, and impaired the anchorage-independent growth of CAOV3 cells. Overexpression of MEF in SKOV3 cells (via retroviral transduction) significantly increased their growth rate, enhanced colony formation in soft agar and promoted tumor formation in nude mice. The oncogenic activity of MEF was further shown by the ability of MEF to transform NIH3T3 cells, and induce their tumor formation in nude mice. MEF is an important regulator of the tumorigenic properties of ovarian cancer cells and could be used a therapeutic target in ovarian cancer.

Mutations in the Nucleolar Phosphoprotein, Nucleophosmin, Promote the Expression of the Oncogenic Transcription Factor MEF/ELF4 in Leukemia Cells and Potentiates Transformation

“…in NIH3T3 cells increases the growth rate, enhances colony formation in soft agar, and promotes tumor formation in nude mice (10). To determine the effects of the interaction of NPM1 with MEF/ELF4 on cell behavior, we assessed the anchorageindependent growth of NIH3T3 cells after co-transfection of MEF/ELF4 with Wt-NPM1 or Mt-A-NPM1.…”

“…MEF/ELF4 is expressed in cancers such as leukemia (9), lymphoma, and ovarian cancer (10). Recently, Totoki et al (11) identified an intrachromosomal inversion (Xq25) in hepatocellular carcinoma that generated a BCORL1-MEF/ELF4 fusion transcript.…”

ELF4 (E74-like factor 4 (ets domain transcription factor))

“…The oncogenic activity of MEF was further shown by the ability of ELF4 to transform NIH3T3 cells, and induce their tumor formation in nude mice (Yao et al, 2007). Thus, ELF4 is an important regulator of the tumorigenic properties of ovarian cancer cells and could be used a therapeutic target in ovarian cancer (Yao et al, 2007).…”

“…ELF4 is expressed in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3 ovarian cancer cell lines, but not in normal ovarian surface epithelium (Yao et al, 2007). Prognosis High levels of ELF4 expression in ovarian cancer are associated with a poor prognosis (Yao et al, 2007). Oncogenesis Manipulating MEF levels in ovarian cancer cell lines alters their behavior; reducing ELF4 levels, using short hairpin RNA expressing vectors, significantly inhibited the proliferation of SKOV3 and CAOV3 cells in culture, and impaired the anchorage-independent growth of CAOV3 cells.…”

“…ELF4 is expressed in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3 ovarian cancer cell lines, but not in normal ovarian surface epithelium (Yao et al, 2007). Prognosis High levels of ELF4 expression in ovarian cancer are associated with a poor prognosis (Yao et al, 2007).…”