A novel gene, CRR9, which was up-regulated in CDDP-resistant ovarian tumor cell line, was associated with apoptosis.

In the screening for cisplatin (CDDP)-resistance related genes by a mRNA differential display method, we detected some increased bands in CDDP resistant ovarian tumor cell line 2008/C13*5.25. One of them, named DD9, was a positive fragment on Northern blot analysis. We cloned it as a full length cDNA by 5'RACE and found a novel gene, CRR9 (Cisplatin Resistance Related gene 9). The CRR9 gene was transcribed into a 2.0 kb mRNA, encoding 512 amino acids. The putative protein had transmembrane-like domains and well conserved on C terminus with human CLPTM1 and the homologs found in Drosophila and C. elegans. Transfection assay showed that the CDDP-sensitive strain 2008 with CRR9 was more sensitive to CDDP, indicating that CRR9 was not associated with the CDDP-resistance, but the CDDP-induced apoptosis.

[1]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[2]  L. Ashworth,et al.  Characterization of a novel gene disrupted by a balanced chromosomal translocation t(2;19)(q11.2;q13.3) in a family with cleft lip and palate. , 1998, Genomics.

[3]  S. Cory,et al.  The Bcl-2 protein family: arbiters of cell survival. , 1998, Science.

[4]  T. Kunkel,et al.  The role of hMLH1, hMSH3, and hMSH6 defects in cisplatin and oxaliplatin resistance: correlation with replicative bypass of platinum-DNA adducts. , 1998, Cancer research.

[5]  N. Saijo,et al.  An active efflux system for heavy metals in cisplatin-resistant human KB carcinoma cells. , 1998, Experimental cell research.

[6]  Y. Fujiwara,et al.  Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs. , 1998, British Journal of Cancer.

[7]  A. V. D. Van Der Zee,et al.  hMLH1 expression and cellular responses of ovarian tumour cells to treatment with cytotoxic anticancer agents , 1997, Oncogene.

[8]  K. Kohno,et al.  A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. , 1996, Cancer research.

[9]  C. Boland,et al.  Loss of DNA mismatch repair in acquired resistance to cisplatin. , 1996, Cancer research.

[10]  D. Lilley,et al.  Human MutScv recognizes damaged DNA base pairs containing 06-methylguanine, 04-methylthymine, or the cisplatin-d(GpG) adduct , 2005 .

[11]  A. Pardee,et al.  Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. , 1992, Science.