Expression of the Elm1 Gene, a Novel Gene of the CCN (Connective Tissue Growth Factor, Cyr61/Cef10, and Neuroblastoma Overexpressed Gene) Family, Suppresses In Vivo Tumor Growth and Metastasis of K-1735 Murine Melanoma Cells

Abstract

We previously isolated a partial cDNA fragment of a novel gene, Elm1 (expressed in low-metastatic cells), that is expressed in low-metastatic but not in high-metastatic K-1735 mouse melanoma cells. Here we determined the full-length cDNA structure of Elm1 and investigated the effect of Elm1 expression on growth and metastatic potential of K-1735 cells. The Elm1 gene encodes a predicted protein of 367 amino acids showing ∼40% amino acid identity with the CCN (connective tissue growth factor [CTGF], Cyr61/Cef10, neuroblastoma overexpressed gene [Nov]) family proteins, which consist of secreted cysteine-rich proteins with growth regulatory functions. Elm1 is also a cysteine-rich protein and contains a signal peptide and four domains conserved in the CCN family proteins. Elm1 was highly conserved, expressed ubiquitously in diverse organs, and mapped to mouse chromosome 15. High-metastatic K-1735 M-2 cells, which did not express Elm1, were transfected with an Elm1 expression vector, and several stable clones with Elm1 expression were established. The in vivo growth rates of cells expressing a high level of Elm1 were remarkably slower than those of cells expressing a low level of Elm1. Metastatic potential of transfectants was reduced in proportion to the level of Elm1 expression. Thus, Elm1 is a novel gene of CCN family that can suppress the in vivo growth and metastatic potential of K-1735 mouse melanoma cells.

Overexpression of a set of genes, including WISP-1, common to pulmonary metastases of both mouse D122 Lewis lung carcinoma and B16-F10.9 melanoma cell lines

“…Furthermore, the mouse WISP-1 is identical to the gene identified as ELM1 (GenBank accession# AB004873). ELM1 is expressed in low, but not high, metastatic mouse melanoma cells, and suppresses the in vivo growth and metastatic potential of K-1735 mouse melanoma cells (Hashimoto et al, 1998). The contradiction between the above findings may be explained in view of previous studies suggesting that the effect of a single gene may differ according to the genetic and cellular context.…”

Identification of an RNA element that confers post-transcriptional repression of connective tissue growth factor/hypertrophic chondrocyte specific 24 (ctgf/hcs24) gene: Similarities to retroviral RNA-protein interactions

“…The abbreviation`CCN' stands for the assemblage of the names of the original members ± ctgf, cef10 and nov. Recently in addition to these, several other genes, such as ctgf-3/ctgf-L/wisp-2/ cop1, wisp-1/elm1, and wisp-3, have been discovered, and newly classi®ed as members of this gene family (Hashimoto et al, 1998;Zhang et al, 1998;Kumar et al, 1999). They are characterized by conserved cysteine residues and modular structure with four distinct domains in primary sequences.…”

The Expression of novH in Adrenocortical Cells Is Down-regulated by TGFβ1 through c-Jun in a Smad-independent Manner

“…The nov 1 gene is a member of the CCN (cyr61 (1), ctgf (2), nov (3,4)) family (5), which also includes elm1/wisp1 (6,7), r-cop1/ wisp2 (6,8,9), and wisp3 (6). It encodes a cysteine-rich secreted multimodular glycoprotein (10), which shares strong structural similarities with the other CCN proteins (5,11).…”