Expression of organic cation transporter SLC22A16 in human epithelial ovarian cancer: a possible role of the adriamycin importer.
The SLC22A16 is one of the newly isolated organic cation transporters, which is responsible for uptake and transport of adriamycin into cells. Adriamycin is considered to be an active agent for ovarian cancer. Recently, the benefit of adding adriamycin to the current standard regimen, paclitaxel and platinum, is evaluated to improve the outcome of patients with ovarian cancer. Therefore, we examined the expression of SLC22A16 in ovarian cancers. Twelve ovarian carcinoma cell lines were used for immunoblotting and reverse transcription-polymerase chain reaction to confirm the expression of SLC22A16 mRNA and protein. Five normal ovaries, 12 ovarian adenomas, and 94 ovarian cancer cases were obtained from patients after surgical therapy. The specimens were used for immunohistochemistry. The median value of relative SLC22A16 gene expression in cell lines derived from clear-cell adenocarcinoma was significantly higher than that in cell lines from other histologies (P < 0.001). Expression of SLC22A16 protein was also detected in cell lines derived from clear-cell adenocarcinoma. The SLC22A16 immunoreactivity was detected in 15 (16%) of 94 epithelial ovarian cancer, 1 (8.3%) of 12 benign adenomas, but 0 (0%) of 5 normal ovary cases. In ovarian cancer tissues, SLC22A16 immunoreactivity was detected in 2 (5%) of 38 serous adenocarcinoma, 1 (6.7%) of 15 endometrioid adenocarcinoma, 0 (0%) of 14 mucinous adenocarcinoma, and 12 (46.2%) of 26 clear-cell adenocarcinoma (P < 0.0001, clear-cell vs other histologies). In conclusion, SLC22A16 was abundantly expressed in clear-cell adenocarcinoma. Our results suggest that adriamycin-related chemicals that are taken up via SLC22A16 may have the potential to be effective against clear-cell adenocarcinoma.
Ota
Kyoko
K
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Ito
Kiyoshi
K
Akahira
Jun-ichi
J
Sato
Naoko
N
Onogawa
Tohru
T
Moriya
Takuya
T
Unno
Michiaki
M
Abe
Takaaki
T
Niikura
Hitoshi
H
Takano
Tadao
T
Yaegashi
Nobuo
N
D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000903:Antibiotics, Antineoplastic; D027701:Organic Cation Transport Proteins; D012334:RNA, Neoplasm; C467737:SLC22A16 protein, human; D004317:Doxorubicin