Isolation and characterization of an estrogen-inhibited variant derived from the MCF-7 breast cancer cell line. 1984

D A Bronzert, and T J Triche, and P Gleason, and M E Lippman

The mechanism by which pharmacological concentrations of estrogen can paradoxically inhibit the growth of human breast cancer is unknown. We have selected for a variant line of MCF-7 which may help to understand this process. The variant was selected by exposing MCF-7 cells to high-specific-activity 16 alpha-[125I]iodoestradiol. These cells were viably frozen for two isotopic half-lives, defrosted once, then reexposed to 16 alpha-[125I]iodoestradiol to allow maximal radiation damage mediated by isotope associated with binding sites. This cell line (113) is one of 55 lines cloned from MCF-7 cells that survived this treatment. The growth response to estradiol of the 113 breast cancer cells grown in monolayer is normal for 4 to 6 days, and then the cell number plateaus as the cells appear to round up and detach. Concomitantly, a decrease in [3H]thymidine incorporation occurs. The cells cannot be rescued by removing estradiol from the medium. The inhibition is dose dependent and can be seen in concentrations of estradiol as low as 10(-10) M. The 113 cells are also inhibited by antiestrogens. They have normal levels of estrogen receptors which bind to DNA cellulose with activation. Progesterone receptors are estrogen inducible, although the levels are one-third that of wild-type MCF-7 cells. The morphological changes determined by electron microscopy of estrogen-treated cells are typical of degenerative cells. To investigate the possibility that inhibitory factors are secreted into the medium by 113 cells, conditioned medium from estrogen-exposed 113 cells is added to normal MCF-7 and 113 cells. No decrease in [3H]thymidine incorporation compared to controls is observed. When the secreted proteins are labeled with [35S]methionine and analyzed by sodium dodecyl sulfate-acrylamide gels, no major differences are apparent in the 113 and MCF-7 cells. Thus, the source of the defect is still unknown. It remains to be seen if the growth-inhibitory effects of 17 beta-estradiol on this cell line are receptor mediated or related to specific gene products which can be identified.

UI MeSH Term Description Entries
D007532 Isoleucine An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels. Alloisoleucine,Isoleucine, L-Isomer,L-Isoleucine,Isoleucine, L Isomer,L-Isomer Isoleucine
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D009363 Neoplasm Proteins Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm. Proteins, Neoplasm
D011960 Receptors, Estrogen Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
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
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002467 Cell Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Cell Nuclei,Nuclei, Cell,Nucleus, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D003600 Cytosol Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components. Cytosols

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