Cisplatin Induction of ERCC-1 mRNA Expression in A2780/CP70 Human Ovarian Cancer Cells

Abstract

cis-Diamminedichloroplatinum (II) (cisplatin)

Inhibition of Gli1 results in altered c-Jun activation, inhibition of cisplatin-induced upregulation of ERCC1, XPD and XRCC1, and inhibition of platinum–DNA adduct repair

“…8 --10 ERCC1 is inducible in human cells. 8 In human ovarian cancer cells, ERCC1 is upregulated after a 1-h treatment with cisplatin. However, a series of events precede the upregulation of ERCC1.…”

“…However, a series of events precede the upregulation of ERCC1. 8,11 After a 1-h cisplatin IC50 (half maximal inhibitory concentration) dose, A2780-CP70 human ovarian cancer cells upregulate the mRNA and protein of c-jun and c-fos. The peak in mRNA levels occurs at 1 --2 h. C-Jun protein is then upregulated, and peaks at 3 --5 h after cisplatin.…”

Molecular mechanisms of cisplatin resistance

“…At least 20 proteins participate in NER, including excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1), a single-strand DNA endonuclease that forms a tight heterodimer with ERCC4 (also known as xeroderma pigmentosum complementation group F (XPF)) and incises DNA on the 5 0 side of bulky lesions such as cisplatin adducts (Biggerstaff and Wood, 1992;Sijbers et al, 1996;Ahmad et al, 2008). Early reports pointed to a correlation between NER proficiency and cisplatin resistance in multiple preclinical models (Li et al, 1998(Li et al, , 2000Metzger et al, 1998), and subsequent studies supported this notion at the clinical level. Thus, ERCC1 expression (be it measured at the mRNA or protein level) has been negatively correlated with survival and/or responsiveness to cisplatin-based regimens in several human neoplasms including bladder (Bellmunt et al, 2007), colorectal (Shirota et al, 2001), gastric (Metzger et al, 1998), esophageal , head and neck (Handra-Luca et al, 2007;Jun et al, 2008) and ovarian cancers (Dabholkar et al, 1992), as well as non-small cell lung cancer (NSCLC) (Olaussen et al, 2006).…”

A modified p53 enhances apoptosis in sarcoma cell lines mediated by doxorubicin

“…Cisplatin is also one of the most widely used chemotherapeutic agents for the treatment of many types of cancer. Apoptosis is the primary mode of cell death induced by cisplatin, and cisplatin occurs primarily through its ability to bind covalently to DNA and prevent DNA replication and transcription (Li et al, 1998;Masuda et al, 1998). The HT1080 cell line is sensitive to doxorubicin , and the present study shows that HT1080 is also more sensitive to cisplatin.…”