Identification of the Yc1 glutathione S-Transferase mRNA as the overexpressed species in a nitrogen mustard–resistant rat mammary carcinoma cell line
✍ Scribed by Nasser Fotouhi-Ardakani; Annie Woo; Marlena Lewandowska; Robyn Schecter; Gerald Batist
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 115 KB
- Volume
- 12
- Category
- Article
- ISSN
- 1095-6670
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✦ Synopsis
Glutathione transferases (GSTs) have been shown to be overexpressed in a number of tumor cell lines selected for resistance to chemotherapeutic drugs and have been implicated in some studies of clinical specimens. In tumor cell lines selected for resistance to chemicals that alkylate DNA, the isoform most frequently overexpressed is GST-Yc, a member of the ␣ class GSTs. To date, two variations of the cDNA designated Yc 1 with subtle differences have been described, and Yc 2 is shown to be clearly distinct. Transfection of a Yc 1 cDNA constitutively expressed in rat liver into rat mammary cancer cells confers resistance to alkylators, however, to a lesser extent than is observed in the cells selected for resistance. It has therefore been widely suggested that the GST that is overexpressed in selected resistant cells represents a distinct and novel isoform. We have previously described a rat mammary carcinoma cell line (MLNr) that is resistant to alkylating agents, and overexpresses a GST with characteristics similar to GST-Yc 1 and not Yc 2 . It has many features common to the several other GST-Yc overexpressing alkylator resistant cell lines. We have cloned the specific Yc cDNA overexpressed in MLNr and analyzed it in detail and found that it is identical to one of the previously reported Yc 1 cDNAs, suggesting that there is no additional Yc gene specifically induced by nitrogen mustards. Another hypothesis to explain the difference in the level of resistance in selected versus GST-Yc transfected cells is the lack of concurrent increased glutathione (GSH) in the transfectants, which is a common feature in the selected resistant cells. Experiments in which we modulated GSH levels suggest that this is not likely. These studies add to our speculation that other mechanisms may be in-