Heterogeneity in androgen receptor levels and growth response to dihydrotestosterone in sublines derived from human hepatocellular carcinoma line (KYN-1).
Heterogeneity in the growth response to androgen and androgen receptor (AR) status in an AR-positive human hepatocellular carcinoma (HCC) line, KYN-1, was investigated in the present study. Seven sublines were obtained from KYN-1 by the limited dilution method. Four of them had no detectable amounts of AR and did not show any growth response to dihydrotestosterone (DHT) at the concentration up to 1000 nM, while the other three had varying amounts of both cytosolic and nucleosolic AR that were 5- to 7-fold higher than that of the parent cell. In the parent cell, the addition of DHT caused a modest but significant increase in the cell number (21%) in a 14-day culture. Such effect was increased by 2- to 7-fold in two AR-positive sublines. In addition, the sensitivity of the response in these two sublines was increased by up to 24-fold. The one remaining AR-positive subline did not show any growth response to DHT, although the behavior of its AR in sucrose gradient ultracentrifugation and Western blotting was the same as that of the other two sublines. These data clearly show that sublines derived from an established human HCC line have a broad heterogeneity in the growth response of HCC to androgen as well as in AR status and could be classified into three groups on the basis of the growth responsiveness to androgen and the AR expression.
Yu
L
L
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Kubota
H
H
Imai
K
K
Yamaguchi
M
M
Nagasue
N
N
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D016895:Culture Media, Serum-Free; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D011944:Receptors, Androgen; D013196:Dihydrotestosterone