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A Novel Gene, CRR9, Which Was Up-Regulated in CDDP-Resistant Ovarian Tumor Cell Line, Was Associated with Apoptosis

https://doi.org/10.1006/bbrc.2001.4250Get rights and content

Abstract

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.

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    As a telomerase regulatory gene, TERT encodes the catalytic subunit of telomerase and plays vital roles in maintaining telomerase expression and facilitating telomeric repeats elongation (Robles-Espinoza et al., 2015). CLPTM1L encodes the cleft lip and palate-associated transmembrane 1 like protein, which is associated with cisplatin-induced apoptosis (Yamamoto et al., 2001). Given the above findings that multiple metals exposure and genetic variations in the TERT-CLPTM1L cluster were both important determinants on telomere length, a critical question of interest is to integrate genome and exposome information in order to understand their combined effects.

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Abbreviations used: ABC, ATP binding cassette; CDDP, cisplatin; GFP, green fluorescent protein; HSP, heat shock protein; MDR, multi drug resistance; MLH, mutL homolog; MSH, mutS homolog; MRP, multi drug resistant protein; RACE, rapid amplification of cDNA ends.

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