Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27

Francesco Acquati, Cristina Morelli, Raffaella Cinquetti, Marco Giorgio Bianchi, Davide Porrini, Liliana Varesco, Viviana Gismondi, Romina Rocchetti, Simona Talevi, Laura Possati, Chiara Magnanini, Maria G. Tibiletti, Barbara Bernasconi, Maria G. Daidone, Vijayalakshmi Shridhar, David I Smith, Massimo Negrini, Giuseppe Barbanti-Brodano, Roberto Taramelli

Research output: Contribution to journalArticle

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Abstract

Cytogenetic, molecular and functional analysis has shown that chromosome region 6q27 harbors a senescence inducing gene and a tumor suppressor gene involved in several solid and hematologic malignancies. We have cloned at 6q27 and characterized the RNASE6PL gene which belongs to a family of cytoplasmic RNases highly conserved from plants, to man. Analysis of 55 primary ovarian tumors and several ovarian tumor cell lines indicated that the RNASE6PL gene is not mutated in tumor tissues, but its expression is significantly reduced in 30% of primary ovarian tumors and in 75% of ovarian tumor cell lines. The promoter region of the gene was unaffected in tumors cell lines. Transfection of RNASE6PL cDNA into HEY4 and SG10G ovarian tumor cell lines suppressed tumorigenicity in nude mice. When tumors were induced by RNASE6PL-transfected cells, they completely lacked expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL-transfected pRPcT1/H6c12T cells, derived from a human/mouse monochromosomic hybrid carrying a human chromosome 6 deleted at 6q27. Moreover, 63.6% of HEY4 clones and 42.8% of the clones of XP12ROSV, a Xeroderma pigmentosum SV40-immortalized cell line, transfected with RNA-SE6PL cDNA, developed a marked senescence process during in vitro growth. We therefore propose that RNASE6PL may he a candidate for the 6q27 senescence inducing and class II tumor suppressor gene in ovarian cancer.

Original languageEnglish (US)
Pages (from-to)980-988
Number of pages9
JournalOncogene
Volume20
Issue number8
DOIs
StatePublished - Feb 22 2001

Fingerprint

Tumor Cell Line
Tumor Suppressor Genes
Organism Cloning
Chromosomes
Carcinoma
Complementary DNA
Genes
Neoplasms
Clone Cells
Xeroderma Pigmentosum
Chromosomes, Human, Pair 6
Human Chromosomes
Hematologic Neoplasms
Ribonucleases
Genetic Promoter Regions
Nude Mice
Cytogenetics
Ovarian Neoplasms
Transfection
RNA

Keywords

  • Chromosome 6q27
  • Class II tumor suppressor gene
  • Ovarian carcinoma
  • Ribonuclease
  • Senescence

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Acquati, F., Morelli, C., Cinquetti, R., Bianchi, M. G., Porrini, D., Varesco, L., ... Taramelli, R. (2001). Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27. Oncogene, 20(8), 980-988. https://doi.org/10.1038/sj.onc.1204178

Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27. / Acquati, Francesco; Morelli, Cristina; Cinquetti, Raffaella; Bianchi, Marco Giorgio; Porrini, Davide; Varesco, Liliana; Gismondi, Viviana; Rocchetti, Romina; Talevi, Simona; Possati, Laura; Magnanini, Chiara; Tibiletti, Maria G.; Bernasconi, Barbara; Daidone, Maria G.; Shridhar, Vijayalakshmi; Smith, David I; Negrini, Massimo; Barbanti-Brodano, Giuseppe; Taramelli, Roberto.

In: Oncogene, Vol. 20, No. 8, 22.02.2001, p. 980-988.

Research output: Contribution to journalArticle

Acquati, F, Morelli, C, Cinquetti, R, Bianchi, MG, Porrini, D, Varesco, L, Gismondi, V, Rocchetti, R, Talevi, S, Possati, L, Magnanini, C, Tibiletti, MG, Bernasconi, B, Daidone, MG, Shridhar, V, Smith, DI, Negrini, M, Barbanti-Brodano, G & Taramelli, R 2001, 'Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27', Oncogene, vol. 20, no. 8, pp. 980-988. https://doi.org/10.1038/sj.onc.1204178
Acquati, Francesco ; Morelli, Cristina ; Cinquetti, Raffaella ; Bianchi, Marco Giorgio ; Porrini, Davide ; Varesco, Liliana ; Gismondi, Viviana ; Rocchetti, Romina ; Talevi, Simona ; Possati, Laura ; Magnanini, Chiara ; Tibiletti, Maria G. ; Bernasconi, Barbara ; Daidone, Maria G. ; Shridhar, Vijayalakshmi ; Smith, David I ; Negrini, Massimo ; Barbanti-Brodano, Giuseppe ; Taramelli, Roberto. / Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27. In: Oncogene. 2001 ; Vol. 20, No. 8. pp. 980-988.
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AU - Acquati, Francesco

AU - Morelli, Cristina

AU - Cinquetti, Raffaella

AU - Bianchi, Marco Giorgio

AU - Porrini, Davide

AU - Varesco, Liliana

AU - Gismondi, Viviana

AU - Rocchetti, Romina

AU - Talevi, Simona

AU - Possati, Laura

AU - Magnanini, Chiara

AU - Tibiletti, Maria G.

AU - Bernasconi, Barbara

AU - Daidone, Maria G.

AU - Shridhar, Vijayalakshmi

AU - Smith, David I

AU - Negrini, Massimo

AU - Barbanti-Brodano, Giuseppe

AU - Taramelli, Roberto

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N2 - Cytogenetic, molecular and functional analysis has shown that chromosome region 6q27 harbors a senescence inducing gene and a tumor suppressor gene involved in several solid and hematologic malignancies. We have cloned at 6q27 and characterized the RNASE6PL gene which belongs to a family of cytoplasmic RNases highly conserved from plants, to man. Analysis of 55 primary ovarian tumors and several ovarian tumor cell lines indicated that the RNASE6PL gene is not mutated in tumor tissues, but its expression is significantly reduced in 30% of primary ovarian tumors and in 75% of ovarian tumor cell lines. The promoter region of the gene was unaffected in tumors cell lines. Transfection of RNASE6PL cDNA into HEY4 and SG10G ovarian tumor cell lines suppressed tumorigenicity in nude mice. When tumors were induced by RNASE6PL-transfected cells, they completely lacked expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL-transfected pRPcT1/H6c12T cells, derived from a human/mouse monochromosomic hybrid carrying a human chromosome 6 deleted at 6q27. Moreover, 63.6% of HEY4 clones and 42.8% of the clones of XP12ROSV, a Xeroderma pigmentosum SV40-immortalized cell line, transfected with RNA-SE6PL cDNA, developed a marked senescence process during in vitro growth. We therefore propose that RNASE6PL may he a candidate for the 6q27 senescence inducing and class II tumor suppressor gene in ovarian cancer.

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