Classification of dependent and autonomous variants of shionogi mammary carcinoma based on heterogenous patterns of androgen binding

Abstract

Eleven variant lines of Shionogi carcinoma cells were screened for dependent or autonomous growth, concentration of cytoplasmic receptor (CR), uptake of androgens into the nucleus (NU) and displaceable nuclear binding (DNB). The results afford a basis for dividing the variant lines into one class of dependent cells and three classes of autonomous cells. Class 1 dependent cells have mean values of CR, 1400 molecules per cell; NU, 6500 molecules per 30 min per nucleus; and DNB, 370 molecules per nucleus. By comparison, class 2 autonomous cells have similar values for CR and NU, but a lower value for DNB (80 molecules per nucleus). Class 3 autonomous cells have uniformly lower values relative to those of class 1 cells (CR, 170 molecules per cell; NU, 400 molecules per 30 min per nucleus; DNB, 40 molecules per nucleus). Class 4 autonomous cells have reduced values for CR and NU, but a DNB value similar to that of class 1 cells. We postulate that the cytoplasmic receptor in class 2 cells fails to become nuclear-bound owing to a defect in the function of the receptor or its acceptor. Conversely, the receptor in class 4 cells appears to become nuclear-bound in the absence of testosterone. Owing to this, the recycling of receptor and the uptake of androgens into the nucleus may be inhibited. Alone, or in combination, the CR and NU phenotypes do not predict for hormonal dependence, but when screening includes a test for DNB, the criteria are sufficient to predict dependence or autonomy for 100% of the tumors.