5′-Deoxy-5′-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines

Fulvio Della Ragione, Gian Luigi Russo, Adriana Oliva, Silvia Mastropietro, Aldo Mancini, Antonella Borrelli, Robert A Casero, Achille Iolascon, Vincenzo Zappia

Research output: Contribution to journalArticle

Abstract

5′-Deoxy-5′methylthioadenosine phosphorylase (MTAPase) gene is localized at the 9p21 region linked to the recently identified putative tumor suppressor gene, p16INK4, which appears implicated in the control of cell division cycle. The phosphorylase is a housekeeping enzyme involved in the purine and amino acid metabolism whose activity is evidentiable in all the normal tissues. Chromosomal deletions encompassing both MTAPase and p16INK4 genes cause the total absence of the enzymatic activity only in malignant cells, thus resulting in defined metabolic differences between malignant and normal cells. MTAPase deficiency was investigated by direct radiochemical assay method and by immunochemical techniques in 35 different human malignant cell lines established from several tumor types. The enzyme-deficient cells derived from breast, lung, ovary and liver cancer, malignant melanomas, malignant gliomas and liposarcomas. Two of the MTAPase-deficient cell preparations (from a liver carcinoma and from a melanoma) are primary cultures thus directly representing the original cancer genotypes. Several of the MTAPase-negative cells were studied for p16INK4 gene deletions and for p16INK4 protein deficiency. In all the examined samples a full correlation exists between the lack of MTAPase and that of p16INK4. A similar result was obtained analysing extracts of Vero cell line, which is a fibroblast MTAPase-negative cell line established from the kidney of a normal adult monkey. Conversely, Cos cells, which also are fibroblasts derived from monkey kidney, show both MTAPase and p16INK4 protein. These results: (i) demonstrate that the phosphorylase deficiency is distributed among almost all the most important human cancers; (ii) confirm and extend the tumor types were p16INK4 gene inactivation is observable and (iii) suggest that deletions at 9p21 (in humans) or at syntenic chromosomes (in other species) might represent a general mechanism of p16INK4 gene loss of function and possibly, in turn, of cancer development and/or progression.

Original languageEnglish (US)
Pages (from-to)827-833
Number of pages7
JournalOncogene
Volume10
Issue number5
StatePublished - Mar 2 1995

Fingerprint

Phosphorylases
Tumor Cell Line
p16 Genes
Cyclin-Dependent Kinase Inhibitor p16
Neoplasms
Cell Line
Haplorhini
Melanoma
Fibroblasts
5'-methylthioadenosine phosphorylase
Kidney
Protein Deficiency
Housekeeping
Liposarcoma
Vero Cells
Gene Deletion
Gene Silencing
Enzymes
Liver Neoplasms
Tumor Suppressor Genes

Keywords

  • 5′-Methylthioadenosine phosphorylase
  • 9p21 chromosome
  • Human cancers
  • p16 gene
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Della Ragione, F., Russo, G. L., Oliva, A., Mastropietro, S., Mancini, A., Borrelli, A., ... Zappia, V. (1995). 5′-Deoxy-5′-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines. Oncogene, 10(5), 827-833.

5′-Deoxy-5′-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines. / Della Ragione, Fulvio; Russo, Gian Luigi; Oliva, Adriana; Mastropietro, Silvia; Mancini, Aldo; Borrelli, Antonella; Casero, Robert A; Iolascon, Achille; Zappia, Vincenzo.

In: Oncogene, Vol. 10, No. 5, 02.03.1995, p. 827-833.

Research output: Contribution to journalArticle

Della Ragione, F, Russo, GL, Oliva, A, Mastropietro, S, Mancini, A, Borrelli, A, Casero, RA, Iolascon, A & Zappia, V 1995, '5′-Deoxy-5′-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines', Oncogene, vol. 10, no. 5, pp. 827-833.
Della Ragione F, Russo GL, Oliva A, Mastropietro S, Mancini A, Borrelli A et al. 5′-Deoxy-5′-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines. Oncogene. 1995 Mar 2;10(5):827-833.
Della Ragione, Fulvio ; Russo, Gian Luigi ; Oliva, Adriana ; Mastropietro, Silvia ; Mancini, Aldo ; Borrelli, Antonella ; Casero, Robert A ; Iolascon, Achille ; Zappia, Vincenzo. / 5′-Deoxy-5′-methylthioadenosine phosphorylase and p16INK4 deficiency in multiple tumor cell lines. In: Oncogene. 1995 ; Vol. 10, No. 5. pp. 827-833.
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AU - Mastropietro, Silvia

AU - Mancini, Aldo

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AU - Casero, Robert A

AU - Iolascon, Achille

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