Senescent WI-38 cells fail to express EPC-1, a gene induced in young cells upon entry into the G0 state

Robert J. Pignolo, Vincent J. Cristofalo, Mitch O. Rotenberg

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Recently we reported the isolation of cDNAs for a number of genes that are differentially expressed between nonproliferating early (young) and late (senescent) population doubling level (PDL) WI-38 human, fetal lung-derived, fibroblast-like cells. We now demonstrate that one of these isolates, EPC-1 (early PDL cDNA-1), derives from an approximately 1.4-kilobase mRNA species that is expressed at a ≥ 100-fold higher level in serum-starved, confluent, young versus similarly treated senescent WI-38 cells. Complete nucleotide sequence analysis of this cDNA confirms its identity with that of a cDNA encoding a secreted, retinal pigmented epithelium differentiation factor as well as similarity of the encoded protein with a number of mammalian serine protease inhibitors. We show that EPC-1 expression is associated with G0 growth arrest in WI-38 cells. The mRNA readily accumulates in density-arrested and/or serum-starved young cells but not in log phase, low density young cells. In contrast, EPC-1 transcript abundance and expression of the encoded, secreted protein are both negligible in senescent WI-38 cells under all culture conditions tested. These findings support the hypothesis that senescent WI-38 cells exhibit a state of growth arrest fundamentally distinct from that of quiescent (G0) young cells.

Original languageEnglish (US)
Pages (from-to)8949-8957
Number of pages9
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Apr 25 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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