TY - JOUR
T1 - Cloning and characterization of a senescence inducing and class II tumor suppressor gene in ovarian carcinoma at chromosome region 6q27
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, Viji
AU - Smith, David I.
AU - Negrini, Massimo
AU - Barbanti-Brodano, Giuseppe
AU - Taramelli, Roberto
N1 - Funding Information:
R Taramelli was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) and MURST Cofin 1998. L Possati and G Barbanti-Brodano were supported by grants from AIRC and MURST ex 60% and Cofin 1998.
PY - 2001/2/22
Y1 - 2001/2/22
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.
AB - 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.
KW - Chromosome 6q27
KW - Class II tumor suppressor gene
KW - Ovarian carcinoma
KW - Ribonuclease
KW - Senescence
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U2 - 10.1038/sj.onc.1204178
DO - 10.1038/sj.onc.1204178
M3 - Article
C2 - 11314033
AN - SCOPUS:17744374767
SN - 0950-9232
VL - 20
SP - 980
EP - 988
JO - Oncogene
JF - Oncogene
IS - 8
ER -