Expression of anionic glutathione S transferase (GSTπ) gene in carcinomas of the uterine cervix and in normal cervices

Abstract

SummaryThe aim of the present study was to analyse in invasive carcinomas of the uterine cervix, the anionic glutathione S transferase (GSTi) gene, possibly implicated in the drug resistance of human cancers. Total RNA preparations obtained from invasive cervical cancers (106 specimens), carcinomas in situ (CIS) (three specimens) and normal cervical epitheliums (24 specimens) were analysed by Northern (Pastan & Gottesman, 1987;Moscow & Cowan, 1988;Endicott & Ling, 1989;D'Arpa & Liu, 1989;Beck, 1989;Giovanella et al., 1989;Tew, 1989 (Beck, 1989;Giovanella et al., 1989). Another mechanism of action involving glutathione S transferase was described in cancer cells resistant to drugs as different as cis-platinum, alkylating agents and anthracyclines (Tew, 1989). The anionic isoenzyme glutathione S transferase (GSTx) which belongs to a complex group of drug-detoxifying enzymes, was present at high levels in the MCF7 breast cancer cell line resistant to Doxorubicine (DXR) together with high levels of MDRI transcripts (Batist et al., 1986;. Although the precise role of GST7 in the development of resistance is not known, its expression may be one among the numerous phenotypic and biochemical changes which accompany drug resistance in some cancers.Patients with invasive carcinoma of the uterine cervix are treated by surgery, radiation and/or chemotherapy (Friedlander et al., 1983;McGuire et al., 1989 Materials and methodsCervical cancers and normal cervical epitheliums One hundred and six specimens of invasive cervical cancer were obtained by biopsy or rarely by surgical excision from untreated patients (93 primary tumours and 5 node metastases) and from treated patients (six recurrent tumours and two liver metastases). These treated patients have received external beam radiotherapy (RX) and/or drug regimen (DR) composed of cis-platinum, Methotrexate, Chlorambucil and Vincristine (Table I). Three specimens of carcinoma in situ (CIS) were also obtained at surgery. Specimens of normal cervical epithelium were obtained from 18 patients treated by surgery for fibroma of the uterine corpus and from six patients with adjacent primary cervical cancers. Tumour and cell samples were immediately stored in liquid nitrogen.DNA and RNA preparations DNAs and total RNAs were prepared from the same tissue samples (about 100 mg) by the guanidinium isothiocyanateCsCl gradient method (Maniatis et al., 1982;Sheng et al., 1990

The expression of placental-type glutathione S-tranferase (GST-?) in human cutaneous squamous cell carcinoma and normal human skin

“…Riou et al [22] reported, on the basis of Northern blot analysis, that although GST-~ is expressed in normal epithelium its expression is enhanced in dysplasia and in carcinoma of the uterine cervix. Also using Northern blot analysis, Konohana et al [13] stated that GST-~ was expressed in the human skin but that no quantitative difference was recognized in the expression of GST-~ between cultured human keratinocytes and the A431 SCC cell line.…”

Glutathione S-transferases and glutathione in human head and neck cancer

“…Moscow et al (22) reported a 7-fold increase in GST-tc mRNA levels in five squamous head and neck cancers as compared with adjacent normal tissue. In addition, Riou et ai (23) found increased levels of GST-ti mRNA in squamous cell carcinomas of the cervix and Eimoto ei ai (24) observed higher GST-ti immunoreactivity in squamous cell carcinomas of the lung when compared with other histological types of lung cancer. In contrast, oesophageal squamous cell carcinomas had lower mean GSTtc concentrations than the surrounding normal tissue, but tumours with much higher GST-tc levels were also found (25).…”