Genetic alterations and chemosensitivity profile in newly established human renal collecting duct carcinoma cell lines.
OBJECTIVE
To determine the genetic alterations and chemosensitivity profile of collecting duct carcinoma (CDC) of the kidney, as it is a rare, highly aggressive malignant tumour with frequent distant metastases.


METHODS
We first established and characterized two human CDC cell lines designated AP3 and AP8, respectively. The CDC cell lines were assessed using microarray-based comparative genomic hybridization and chemosensitivity testing.


RESULTS
The CDC cells grew in vitro as an adherent monolayer with epithelial morphology, but had different growth rates. The cell lines had the characteristic immunophenotype of CDC (high molecular weight cytokeratin-+ve/cytokeratin 7-+ve/vimentin-+ve). Both cell lines shared copy number gains in chromosomes 20 and X. The loci showing a copy number gain were SOX22 at 20p tel, topoisomerse I (TOP1) at 20q12-q13.1, TPD52L2 at 20q tel, 20QTEL14 at 20q tel, KAL at Xp22.3, STS 5' at Xp22.3, OCRL1 at Xq25, AR3'at Xq11-q12, and XIST at Xq13.2, respectively. Immunoblot analysis confirmed that the AP3 and AP8 cell lines showed moderate and high levels of TOP1 expression, respectively. By chemosensitivity testing, the AP8 cells were most sensitive to topoisomerase I and II inhibitors such as topotecan, epirubicin and doxorubicin, but the AP3 cells did not. The chemosensitivity to these drugs was paralleled by cell death via apoptosis.


CONCLUSIONS
The results suggest that TOP1 might be one of the molecular targets in AP8 CDC cells. Thus, these novel CDC cell lines will be useful for discovering therapeutic targets and developing effective anticancer drugs against CDC.
Wu
Zheng-Sheng
ZS
Department of Pathology, Korea University Ansan Hospital, Ansan, Korea.
Lee
Ju-Han
JH
Kwon
Jung-Ah
JA
Kim
Seo-Hee
SH
Han
Sun-Hee
SH
An
Jung-Suk
JS
Lee
Ji-Hye
JH
Lee
Eung-Seok
ES
Park
Heum-Rye
HR
Kim
Young-Sik
YS
D000368:Aged; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics*; D007685:Kidney Tubules, Collecting; D008297:Male; D008875:Middle Aged
D004264:DNA Topoisomerases, Type I