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) li ne, KYN-1, was investigated in the present study. Seven sublines were obtained from KYN-1 by the limited dilution method. Four of them had n o detectable amounts of AR and did not show any growth response to dih ydrotestosterone (DHT) at the concentration up to 1000 nM, while the o ther three had varying amounts of both cytosolic and nucleosolic AR th at were 5- to 7-fold higher than that of the parent cell. In the paren t cell, the addition of DHT caused a modest but significant increase i n 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 sensiti vity of the response in these two sublines was increased by up to 24-f old. The one remaining AR-positive subline did not show any growth res ponse to DHT, although the behavior of its AR in sucrose gradient ultr acentrifugation and Western blotting was the same as that of the other two sublines. These data clearly show that sublines derived from an e stablished human HCC line have a broad heterogeneity in the growth res ponse of HCC to androgen as well as in AR status and could be classifi ed into three groups on the basis of the growth responsiveness to andr ogen and the AR expression.