β4 Integrin subunit expression is downregulated in low metastatic carcinoma variants

L. Cimino, D. Perrotti, G. D'Agostino, R. Falcioni, A. Sacchi

Research output: Contribution to journalArticlepeer-review

Abstract

Organization and expression of the gene coding for β4 integrin subunit were investigated in murine carcinoma lines endowed with low and high metastatic potential maintained both in vivo and in vitro. Probes corresponding to either the extracellular or the cytoplasmic domains of the protein were generated and employed for Southern and Northern blot hybridization experiments. Southern blot analysis demonstrates a restriction fragment length polymorphism between BALB/c and C57BI/6J DNAs. The different genomic organization of the β4 gene apparently does not generate variation in mRNA length. Northern blot analysis reveals a 7-kb transcript encoding full-length β4 protein and shorter transcripts that apparently correspond to nonfunctional mRNAs. In carcinoma cells endowed with low metastatic capacity, the 7-kb mRNA cannot be revealed in spite of the presence of shorter transcripts. In contrast, the 7-kb transcript is always present in tumor cells endowed with high metastatic capacity. Accordingly, the β4 protein is detectable, either by immunofluorescence or by Western blot analyses, only in highly metastatic carcinoma cells. In conclusion, the data presented show that in these murine carcinoma cell lines (i) the 7-kb mRNA is associated with a more invasive phenotype, and (ii) missing expression of the β4 integrin subunit in low metastatic carcinoma cells depends, at least in part, on mechanisms acting at a post-transcriptional level. The possibility that β4 subunit expression is a consequence of specific differentiation stages of lung carcinoma cells is discussed.

Original languageEnglish
Pages (from-to)158-166
Number of pages9
JournalCancer Detection and Prevention
Volume21
Issue number2
Publication statusPublished - 1997

Keywords

  • gene expression
  • integrin
  • metastases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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