Biomaterial Database

Regulation of epidermal growth factor receptor levels by 1,25-dihydroxyvitamin D3 in human breast cancer cells. 1988

M Koga, and J A Eisman, and R L Sutherland

Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, NSW, Australia.

Specific, high affinity receptors for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have been demonstrated in human breast cancer cells. In addition, 1,25-(OH)2D3 has been shown to inhibit replication in some human breast cancer cell lines, although the mechanism(s) of this anti-tumor activity remain undefined. There is currently considerable interest in the role of autocrine growth factors in the control of breast cancer cell proliferation and the effects of steroid hormones on their production, receptor binding, and action. Since the epidermal growth factor (EGF) receptor mediates the effects of both EGF and the autocrine growth factor, alpha-transforming growth factor, we investigated the effect of 1,25-(OH)2D3 on EGF receptor levels in several human breast cancer cell lines. Preincubation of T-47D cells with 1,25-(OH)2D3 for 24 h resulted in a significant concentration-dependent decline in the specific binding of [125I]EGF. The effect was observed when EGF binding was assayed at either 0 or 37 degrees C, both before and after treatment with acid to remove receptor bound endogenous ligand. This indicated that the effect on [125I]-EGF binding was not due to effects of 1,25-(OH)2D3 on receptor internalization and degradation or receptor occupancy. The half-maximal inhibitory concentration of 1,25-(OH)2D3 was approximately 2 nM. The decrease in EGF binding was due to a decrease in receptor number from 2,900 sites/cell in control cultures to 2,330 and 1,730 sites/cell in cells treated for 24 h with 10(-8) and 10(-6) M 1,25-(OH)2D3, respectively. There was no change in the affinity of the receptor for EGF following treatment with 1,25-(OH)2D3 [Kd = 0.075 +/- 0.006 nM (+/- SEM) for control and Kd = 0.083 +/- 0.004 nM for treated cells]. Decreased EGF receptor levels were also achieved with a number of analogues of 1,25-(OH)2D3 in accordance with their affinities for the 1,25-(OH)2D3 receptor, i.e., potencies for decreasing EGF binding in T-47D cells were in the order: 1,25-(OH)2D3 greater than 1,24,25-trihydroxyvitamin D3 greater than 1,25,26-trihydroxyvitamin D3 greater than 24,25-dihydroxyvitamin D3 greater than or equal to 25-hydroxyvitamin D3. Specific, saturable EGF binding to MCF-7 cells was also reduced by 1,25-(OH)2D3 while binding to BT-20 and HBL-100 cells was unaffected by this treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

UI	MeSH Term	Description	Entries
D011372	Progestins	Compounds that interact with PROGESTERONE RECEPTORS in target tissues to bring about the effects similar to those of PROGESTERONE. Primary actions of progestins, including natural and synthetic steroids, are on the UTERUS and the MAMMARY GLAND in preparation for and in maintenance of PREGNANCY.	Gestagenic Agent,Progestagen,Progestagenic Agent,Progestational Agent,Progestational Compound,Progestational Hormone,Progestogen,Progestogens,Gestagen,Gestagen Effect,Gestagen Effects,Gestagenic Agents,Gestagenic Effect,Gestagenic Effects,Gestagens,Progestagenic Agents,Progestagens,Progestational Agents,Progestational Compounds,Progestational Hormones,Progestin,Progestin Effect,Progestin Effects,Progestogen Effect,Progestogen Effects,Agent, Gestagenic,Agent, Progestagenic,Agent, Progestational,Compound, Progestational,Effect, Gestagen,Effect, Gestagenic,Effect, Progestin,Effect, Progestogen,Effects, Gestagen,Effects, Gestagenic,Effects, Progestin,Effects, Progestogen,Hormone, Progestational
D011987	Receptors, Steroid	Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.	Corticosteroid Receptors,Receptors, Corticosteroid,Steroid Receptors,Corticosteroid Receptor,Receptors, Steroids,Steroid Receptor,Receptor, Corticosteroid,Receptor, Steroid,Steroids Receptors
D001943	Breast Neoplasms	Tumors or cancer of the human BREAST.	Breast Cancer,Breast Tumors,Cancer of Breast,Breast Carcinoma,Cancer of the Breast,Human Mammary Carcinoma,Malignant Neoplasm of Breast,Malignant Tumor of Breast,Mammary Cancer,Mammary Carcinoma, Human,Mammary Neoplasm, Human,Mammary Neoplasms, Human,Neoplasms, Breast,Tumors, Breast,Breast Carcinomas,Breast Malignant Neoplasm,Breast Malignant Neoplasms,Breast Malignant Tumor,Breast Malignant Tumors,Breast Neoplasm,Breast Tumor,Cancer, Breast,Cancer, Mammary,Cancers, Mammary,Carcinoma, Breast,Carcinoma, Human Mammary,Carcinomas, Breast,Carcinomas, Human Mammary,Human Mammary Carcinomas,Human Mammary Neoplasm,Human Mammary Neoplasms,Mammary Cancers,Mammary Carcinomas, Human,Neoplasm, Breast,Neoplasm, Human Mammary,Neoplasms, Human Mammary,Tumor, Breast
D002117	Calcitriol	The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.	1 alpha,25-Dihydroxycholecalciferol,1 alpha,25-Dihydroxyvitamin D3,1, 25-(OH)2D3,1,25(OH)2D3,1,25-Dihydroxycholecalciferol,1,25-Dihydroxyvitamin D3,1 alpha, 25-dihydroxy-20-epi-Vitamin D3,1,25(OH)2-20epi-D3,1,25-dihydroxy-20-epi-Vitamin D3,20-epi-1alpha,25-dihydroxycholecaliferol,Bocatriol,Calcijex,Calcitriol KyraMed,Calcitriol-Nefro,Decostriol,MC-1288,MC1288,Osteotriol,Renatriol,Rocaltrol,Silkis,Sitriol,Soltriol,Tirocal,1 alpha,25 Dihydroxyvitamin D3,1,25 Dihydroxycholecalciferol,1,25 Dihydroxyvitamin D3,1,25 dihydroxy 20 epi Vitamin D3,Calcitriol Nefro,D3, 1 alpha,25-Dihydroxyvitamin,D3, 1,25-Dihydroxyvitamin,D3, 1,25-dihydroxy-20-epi-Vitamin,KyraMed, Calcitriol,MC 1288
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013006	Growth Hormone	A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.	Growth Hormone, Recombinant,Pituitary Growth Hormone,Recombinant Growth Hormone,Somatotropin,Somatotropin, Recombinant,Growth Hormone, Pituitary,Growth Hormones Pituitary, Recombinant,Pituitary Growth Hormones, Recombinant,Recombinant Growth Hormones,Recombinant Pituitary Growth Hormones,Recombinant Somatotropins,Somatotropins, Recombinant,Growth Hormones, Recombinant,Recombinant Somatotropin
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D018167	Receptors, Calcitriol	Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors.	Calcitriol Receptors,Cholecalciferol Receptors,Receptors, Vitamin D,Vitamin D 3 Receptors,Vitamin D Receptors,1,25-Dihydroxycholecalciferol Receptor,1,25-Dihydroxycholecalciferol Receptors,1,25-Dihydroxyvitamin D 3 Receptor,1,25-Dihydroxyvitamin D3 Receptor,1,25-Dihydroxyvitamin D3 Receptors,Calcitriol Receptor,Receptors, 1,25-Dihydroxyvitamin D 3,Receptors, Cholecalciferol,Receptors, Vitamin D 3,Receptors, Vitamin D3,Vitamin D 3 Receptor,Vitamin D Receptor,Vitamin D3 Receptor,Vitamin D3 Receptors,1,25 Dihydroxycholecalciferol Receptor,1,25 Dihydroxycholecalciferol Receptors,1,25 Dihydroxyvitamin D 3 Receptor,1,25 Dihydroxyvitamin D3 Receptor,1,25 Dihydroxyvitamin D3 Receptors,D Receptor, Vitamin,D Receptors, Vitamin,D3 Receptor, 1,25-Dihydroxyvitamin,D3 Receptor, Vitamin,D3 Receptors, 1,25-Dihydroxyvitamin,D3 Receptors, Vitamin,Receptor, 1,25-Dihydroxycholecalciferol,Receptor, 1,25-Dihydroxyvitamin D3,Receptor, Calcitriol,Receptor, Vitamin D,Receptor, Vitamin D3,Receptors, 1,25-Dihydroxycholecalciferol,Receptors, 1,25-Dihydroxyvitamin D3
D066246	ErbB Receptors	A family of structurally related cell-surface receptors that signal through an intrinsic PROTEIN-TYROSINE KINASE. The receptors are activated upon binding of specific ligands which include EPIDERMAL GROWTH FACTORS, and NEUREGULINS.	EGF Receptor,Epidermal Growth Factor Receptor,Epidermal Growth Factor Receptor Family Protein,Epidermal Growth Factor Receptor Protein-Tyrosine Kinase,ErbB Receptor,HER Family Receptor,Receptor, EGF,Receptor, Epidermal Growth Factor,Receptor, TGF-alpha,Receptor, Transforming-Growth Factor alpha,Receptor, Urogastrone,Receptors, Epidermal Growth Factor-Urogastrone,TGF-alpha Receptor,Transforming Growth Factor alpha Receptor,Urogastrone Receptor,c-erbB-1 Protein,erbB-1 Proto-Oncogene Protein,EGF Receptors,Epidermal Growth Factor Receptor Family Proteins,Epidermal Growth Factor Receptor Kinase,HER Family Receptors,Proto-oncogene c-ErbB-1 Protein,Receptor Tyrosine-protein Kinase erbB-1,Receptor, ErbB-1,Receptors, Epidermal Growth Factor,Epidermal Growth Factor Receptor Protein Tyrosine Kinase,ErbB-1 Receptor,Family Receptor, HER,Family Receptors, HER,Proto oncogene c ErbB 1 Protein,Proto-Oncogene Protein, erbB-1,Receptor Tyrosine protein Kinase erbB 1,Receptor, ErbB,Receptor, ErbB 1,Receptor, HER Family,Receptor, TGF alpha,Receptor, Transforming Growth Factor alpha,Receptors, EGF,Receptors, Epidermal Growth Factor Urogastrone,Receptors, ErbB,Receptors, HER Family,c erbB 1 Protein,c-ErbB-1 Protein, Proto-oncogene,erbB 1 Proto Oncogene Protein