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

Cytogenetic, molecular and functional analysis has shown that chromosome re gion 6q27 harbors a senescence inducing gene and a tumor suppressor gene in volved in several solid and hematologic malignancies. We have cloned at 6q2 7 and characterized the RNASE6PL gene which belongs to a family of cytoplas mic RNases highly conserved from plants, to man. Analysis of 55 primary ova rian tumors and several ovarian tumor cell lines indicated that the RNASE6P L 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 line s suppressed tumorigenicity in nude mice. When tumors were induced by RNASE 6PL-transfected cells, they completely lacked expression of RNASE6PL cDNA. Tumorigenicity was suppressed also in RNASE6PL-transfected pRPcT1/ H6c12T c ells, derived from a human/mouse monochromosomic hybrid carrying a human ch romosome 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, t ransfected with RNASE6PL cDNA, developed a marked senescence process during in vitro growth. We therefore propose that RNASE6PL may be a candidate for the 6q27 senescence inducing and class II tumor suppressor gene in ovarian cancer.