Characterization of prolactin receptors and their distribution among American and Israeli women with breast cancer: implications for prediction of hormonal dependency and treatment.

A micro-method is reported for the determination and characterization of prolactin (PRL) receptors in human breast cancer specimens using either intact biopsy tissue or the pellet fraction remaining from biopsies previously processed for steroid hormone receptors. Labeled human PRL is used as the ligand. The specific PRL-binding of 307 human breast cancer specimens was evaluated by this micro-method. A significant level of specific PRL-binding (3-25 fmol per mg membrane protein) was detected in 41% of US breast cancer patients and 42% of Israeli patients. Scatchard analyses, performed on pooled membrane fractions with the highest specific PRL-binding revealed one class of receptors having a dissociation constant, Kd = 4.1 x 10(-9), and specific binding capacity, Bmax = 1.3 pmol per mg protein. These preparations were exposed to 3 M MgCl2, which dissociates the endogenous-bound PRL from the hormone-receptor complex and allows the characterization of the "total" PRL receptors. Two classes of receptors were then revealed. One class of receptors showed high affinity (Kd1 = 8.1 x 10(-10) M) and low capacity (Bmax1 = 335 fmol per mg protein), while the other possessed lower affinity (Kd2 = 8.2 x 10(-8) M), but a higher capacity (Bmax2 = 34.4 pmol per mg protein). Since PRL facilitates the growth of human breast cancer cell lines, these results indicate that a high proportion of human breast cancers may be PRL dependent. Routine determination of PRL receptors in biopsies of human breast cancer may permit the selection of a better treatment, since it is possible that the reduction in PRL levels could inhibit those tumors which are prolactin dependent.