Multidrug resistance gene 1 expression in salivary gland adenocarcinomas and oral squamous-cell carcinomas.
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.
Uematsu
T
T
Department of Oral and Maxillofacial Surgery, Matsumoto Dental University School of Dentistry, Shiojiri, Nagano 399-0781, Japan.
Hasegawa
T
T
Hiraoka
B Y
BY
Komatsu
F
F
Matsuura
T
T
Yamada
A S
AS
Yamaoka
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000627:therapeutic use*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D014750:Vincristine