ヒト乳癌の性ステロイド反応性の指標に関する研究
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This study was designed to obtain indicators for endocrine responsiveness in human breast cancer. In this study steroid receptors in breast cancer tissue were first characterized as follows : estradiol-17β (E<SUB>2</SUB>) -estrogen receptor (ER) had a dissociation constant (Kd) of 5.50 ± 0.39 × 10<SUP>-10</SUP>M in premenopause or 5.60 ± 0.43 × 10<SUP>-10</SUP>M in postmenopause, R5020progesterone receptor (PR) had a Kd of 4.80 ± 0.63 × 10<SUP>-10</SUP>M in premenopause or 4.20 ± 0.40 × 10<SUP>-10</SUP>M in postmenopause, 5α-dihydrotestosterone (DHT) -androgen receptor (AR) had a Kd of 5.04 ± 0.55 × 10<SUP>-10</SUP>M in premenopause or 4.12 ± 0.47 × 10<SUP>-10</SUP>M in postmenopause, and R1881-AR had a Kd of 2.90 ± 0.50 × 10<SUP>-10</SUP>M, determined by charcoal adsorption at 4°C. Such steroid receptors were sedimented to 7-6S and 5-4S regions, and the 7-6S binding was easily dissociated during 5-20 percent sucrose gradient centrifugation. R1881-cytosol bindings contained AR and PR. Cytosolic steroid receptor levels were determined in each case. Maximal binding sites (Bm; fmol/mg cytosol protein) analyzed by Scatchard plots analysis were as follows : 65.6 ± 11.4 (premenopause) and 81.0 ± 17.1 (postmenopause) in ER (NS), 19.2 ± 4.4 (premenopause) and 44.4 ± 10.3 (postmenopause) in PR (p<0.05), 71.6 ± 17.6 (premenopause) and 77.9 ± 12.1 (postmenopause) in AR (DHT) (NS), and 25.3 ± 7.5 (premenopause) and 14.4 ± 9.5 (postmenopause) in AR (R1881) (NS). The nuclear receptor was determined by exchange assay. Nuclear PR and AR were detected in few cases. Nuclear ER was detected where in some cases cytosolic ER was not detected. The necessity of determining nuclear ER whenever ER is present or absent in the tumor cell will be discussed.<BR>In examining the nuclear binding of a steroid receptor complex, the ER and PR of rabbit uterine cytosol were substituted for those of breast cancer tissues. The nuclear binding was dependent upon the dose and incubation time of the rabbit-steroid uterine cytosol complex. The dissociation constant of the nuclear binding of the E<SUB>2</SUB>-ER complex was 6.1 × 10<SUP>-11</SUP>M, and that of the R5020-PR complex was 1.5 × 10<SUP>-10</SUP>M in a case. In determined cases, even when the ER or PR was present in either the cytoplasm or nucleus of the tumor cell, the steroid-receptor complex formed in the rabbit uterine cytosol did not bind to the tumor nuclei in some cases. These results suggest that part or all of the nuclear receptor-binding sites of breast cancer tissues are defective in some tumor nuclei.<BR>When the E<SUB>2</SUB> -ER complex bound to the tumor nuclei, the nuclear RNA synthesis was stimulated in the time-dependent process of the E<SUB>2</SUB>-ER complex. Through the determined cases, even when the E<SUB>2</SUB>-ER complex bound to the tumor nuclei, the nuclear RNA synthesis was not stimulated in some cases.<BR>The above results suggest that the presence of a steroid receptor, the nuclear binding of a steroid-receptor complex, or the stimulation of nuclear RNA synthesis by steroid receptors occurring in breast cancer cells are more precise indicators of endocrine responsiveness in human breast cancer.
- 一般社団法人 日本内分泌学会の論文
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