Correlation of lactogenic receptor concentration in human breast cancer with estrogen receptor concentration

Abstract

The presence of receptors for lactogenic hormones in human breast cancer tissue has been documented previously, but the relationship between the expression of these receptors and estrogen receptor (ER) status has not been adequately studied. In this report, the specificity of 125I-human growth hormone (HGH) binding in both cultured human breast cancer cell lines and tumor biopsies was studied to establish that HGH was a suitable ligand for investigating lactogenic receptor concentration in these tissues. In addition, the relationship between specific binding of 125I-HGH and ER concentration in human breast cancer was investigated. Specific 125I-HGH binding to 14 breast cancer cell lines in long term culture and to membrane preparations (microsomal and plasma membrane fractions) from 31 breast cancer biopsy specimens was examined. Human prolactin and HGH were approximately equipotent in inhibiting binding of 125I-HGH to both cultured breast cancer cell lines and to membrane preparations from breast cancer biopsy specimens. Competitive inhibition experiments using lactogenic and somatogenic hormones established that the specificity of 125I-HGH binding to breast cancer biopsy material was similar to that of cultured breast cancer cell lines and similar to that reported for subprimate lactogenic receptors. Saturable, high-affinity (Ka = 0.53 to 2.33 nM-1), low-capacity (330 to 6560 sites/cell) growth hormone binding sites were found on each of the ER-positive cell lines, whereas no specific 125I-HGH binding to ER-negative cell monolayers was detected. When all cell lines were considered, a significant linear correlation (r = 0.745, p less than 0.001) between ER and lactogenic receptor concentrations was found. Significant specific 125I-HGH binding, greater than 1% of the total radioactivity added, was detected in 20 of 31 (65%) breast tumor biopsy specimens. The mean affinity and capacity of the lactogenic receptor as measured in 8 separate membrane preparations were Ka = 0.52 +/- 0.09 (S.E.) nM-1 and 255 +/- 85 fmol/mg protein. Membrane preparations from ER-negative tumors (less than 3 fmol ER/mg cytosol protein) bound significantly less 125I-HGH than did membrane preparations from ER-positive tumor biopsies (1.22 +/- 0.44 versus 3.21 +/- 0.56%, p less than 0.05). A significant linear correlation between specifically bound 125I-HGH and ER concentration (r = 0.412, p less than 0.02) was demonstrated in the 31 breast cancer biopsy specimens studied.(ABSTRACT TRUNCATED AT 400 WORDS)