The expression of 'tissue' transglutaminase in two human cancer cell lines is related with the programmed cell death (apoptosis)

M. Piacentini, L. Fesus, M. G. Farrace, L. Ghibelli, L. Piredda, G. Melino

Research output: Contribution to journalArticle

Abstract

The expression of 'tissue' transglutaminase (tTG) in two human tumor cell lines (the cervix adenocarcinoma line HeLa-TV and the neuroblastoma cells SK-N-BE-2) was found to be in correlation with the rate of physiological cell death (apoptosis) in culture. We investigated the effect of retinoic acid (RA) and α-difluoromethylornithine (DFMO) in order to elucidate the relationship between tTG expression and apoptosis. RA led to a 6-fold increase of tTG activity in HeLa-TV cells and to a 12-fold increase in SK-N-BE(2) cells, which was paralleled in both cell lines by a proportional increase in the number of apoptotic bodies recovered from the cultures. On the contrary, DFMO determined a dramatic reduction of tTG expression and of the apoptotic index. Immunohistochemical analysis using an anti-tTG antibody showed that the enzyme was accumulated in both cell lines within typical apoptotic bodies. Immunocytochemistry and cell cloning of SK-N-BE(2) line demonstrated that tTG was absent in cells showing neurite outgrowth, indicating that the enzyme expression is not associated with neural differentiation, even though both phenomena are elicited by retinoic acid. On the whole, these data indicate that also in tumors tTG activation takes place in cells undergoing apoptosis. The enzyme is activated in apoptotic cells to form cross-linked protein envelopes which are insoluble in detergents and chaotropic agents. The number of insoluble protein envelopes as well as the N,N-bis(γ-glutamyl)polyamine cross-links is related with both tTG expression and apoptotic index, strongly suggesting the participation of the enzyme in the apoptotic program. Hence, we propose that the antitumoral activity of RA is due at least in part to the induction of apoptosis.

Original languageEnglish
Pages (from-to)246-254
Number of pages9
JournalEuropean Journal of Cell Biology
Volume54
Issue number2
Publication statusPublished - 1991

Keywords

  • α-difluoromethylornithine (DFMO)
  • di- and polyamine γ-glutamyl derivatives
  • HeLa
  • neuroblastoma
  • polyamines
  • retinoic acid

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

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