Suppression of human ribosomal protein L23A expression during cell growth inhibition by interferon-β

Abstract

Interferons inhibit cell growth in normal and tumorderived cells. The molecular basis of interferons antiproliferative activity remains to be de®ned. Using subtraction hybridization, a human melanoma dierentiation associated gene, mda-20, has been identi®ed that is down-regulated by treatment with interferon. Sequence analysis indicates that mda-20 is human ribosomal protein L23a (rp L23a). The mRNA levels of rp L23a and growth are diminished in a variety of human tumor cell lines following treatment with human ®broblast interferon, interferon-b (IFN-b). Expression of rp L23a is also reduced in human melanoma cells treated with human leukocyte (IFN-a) and immune (IFN-g) interferons, but not by growth inhibition resulting from serum starvation. These ®ndings suggest that growth suppression alone is not sucient to reduce rp L23a expression. Instead, reduced rp L23a mRNA results from biochemical changes mediated by interferons. Ectopic expression of an antisense rp L23a sequence in human HeLa cervical carcinoma cells results in a reduction in colony formation indicating a direct antiproliferative eect by inhibiting rp L23a expression. The mechanism underlying inhibition in rp L23a expression in IFN-b-treated cells may involve antisense rp L23a RNA. These results suggest that rp L23a may be one of the target molecules involved in mediating growth inhibition by interferon.

Anti-inflammatory action of type I interferons deduced from mice expressing interferon β

“…26,27,34,35 Among type I IFNs, IFN-␤ has potent antiproliferative activity against most human tumor cells in vitro in addition to its known immunomodulatory activities. [36][37][38][39][40] For these reasons, the availability of an animal model expressing IFN-␤ might help to understand the biological properties of this cyto- …”

Suppression subtractive hybridization and expression profiling identifies a unique set of genes overexpressed in non-small-cell lung cancer

“…LDB1 is overexpressed in oral carcinoma (Mizunuma et al, 2003). Ribosomal proteins RPL8 (Tarantul et al, 2000), RPS13 (Denis et al, 1993), RPL5 (Frigerio et al, 1995), RPL23A (Jiang et al, 1997), RPL19 (Henry et al, 1993), RPL37 (Loging and Reisman, 1999), and RPS16 (Batra et al, 1991) are previously reported in association with multiple cancers other than NSCLC. Our data illustrate the success of our approach in discovering previously unidentified NSCLC-specific genes.…”

Identification and temporal expression pattern of genes modulated during irreversible growth arrest and terminal differentiation in human melanoma cells

“…If any or all of these genes are direct regulators of dierentiation, growth or the tumorigenic process then ectopically expressing these genes, using sense or inducible sense expression constructs (Jiang et al, 1995a(Jiang et al, ,c, 1996b(Jiang et al, , 1997, or blocking expression of these genes, using antisense or ribozyme based technologies (Alama et al, 1997;Su et al, 1998a), may directly modify these phenotypes in melanoma cells. Further studies designed to characterize the presently identi®ed DISH genes and to identify the remaining gene expression changes regulated as a function of induction of de®ned phenotypic changes in human melanoma cells are well warranted.…”