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Multidrug resistance gene 1 expression in salivary gland adenocarcinomas and oral squamous‐cell carcinomas
Author(s) -
Uematsu Takashi,
Hasegawa Takafumi,
Hiraoka B. Yukihiro,
Komatsu Fuhito,
Matsuura Takashi,
Yamada AkiSato,
Yamaoka Minoru
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200102)9999:9999<::aid-ijc1180>3.0.co;2-t
Subject(s) - p glycoprotein , salivary gland , cancer , multiple drug resistance , cell culture , cancer research , pathology , immunohistochemistry , epidermoid carcinoma , cancer cell , salivary gland cancer , chemotherapy , biology , medicine , drug resistance , genetics , microbiology and biotechnology
In combined chemotherapy for head‐and‐neck cancer (HNC), salivary gland‐cell adenocarcinoma (SGA) shows insufficient clinical outcome, and it has been suggested that the sensitivity and/or the mechanism of resistance to anti‐cancer drugs are different between SGA and oral squamous‐cell carcinoma (SCC). The aim of our study was to clarify whether P‐glycoprotein (P‐gp) expression is associated with multidrug resistance (MDR) in HNC and the difference in the process of its development between SGA and SCC. In immunohistochemical analysis, P‐gp expression was found in the ductal cells of salivary glands but not in oral mucosal epithelium. In cancer tissues, a few SCC cells in 12 of 37 and most cells in all SGAs expressed P‐gp. The intensive P‐gp expression was significantly found in SGA compared with SCC. In an in vivo chemotherapeutic model using tumor‐bearing nude mice, P‐gp expression in counterparts was observed in only a few cells of the HSY line, while no P‐gp expression was observed in Hepd cells. However, P‐gp expression was developed in both HSY and Hepd cell lines after vincristine (VCR) treatment. RT‐PCR showed that the mean ratios of mdr1 mRNA expression levels in HSY clones were 3.7‐fold higher than those in Hepd clones after VCR treatment, while each cell line exhibited both induction and activated production of P‐gp. These results suggest that P‐gp–related MDR in SGA is an inherent phenotype caused by both high levels of P‐gp induction and activated P‐gp production during VCR treatment, while that in SCC is an acquired phenotype chiefly caused by induction of P‐gp. © 2001 Wiley‐Liss, Inc.