Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Demineralized extracts of bone matrix and conditioned media from cultured fetal rat calvaria have been reported to contain growth stimulatory activity for bone cells. To investigate the potential role of these local bone growth factors in the development of bone metastases, we chose the Walker 256 carcinosarcoma, a rat mammary tumor which causes osteolytic bone metastases and hypercalcemia. 45Ca-labeled, 19-day fetal Sprague-Dawley rat calvaria were cultured for 96 hours in BGJb medium. Walker cells from ascites tumors or cultures were grown in unconditioned media or in conditioned media harvested from the bone cultures, in the presence of 10% fetal calf serum. Media were changed every 2 days, cells were counted daily for 5 days, and 3H-thymidine uptake into acid insoluble residues was measured. The growth of tumor cells was 5-6-fold greater in conditioned media than in unconditioned media and the effect was dose dependent. Cells cultured in conditioned media demonstrated a approximately 3-fold enhancement of 3H-thymidine incorporation. Generation of growth stimulatory activity correlated with the extent of bone resorption, measured by release of 45Ca from the fetal parietal bones (r = 0.85; P less than 0.001). Conditioned media from bones cultured with 10(-7) M prostaglandin E2 (PGE2) contained greater amounts of growth stimulatory activity than untreated conditioned media, but PGE2 itself did not stimulate tumor cell growth. Addition of 3.5 mM PO4 to bone cultures blocked bone resorption and the generation of growth factors. Growth stimulatory activity was stable to heat (56 C for 30 minutes) and trypsin digestion, with an apparent molecular weight of less than 17,000 daltons by high-performance liquid chromatography. Conditioned medium also stimulated the growth of 13762 rat mammary adenocarcinoma cells, MB-MDA-231 human breast carcinoma cells, TE-85 osteosarcoma cells, a murine fibrosarcoma and rat embryonic fibroblasts, with the most potent effects noted for Walker tumor cells, the TE-85 osteosarcoma, and human breast carcinoma lines. These results suggest a mechanism by which bone resorption could promote the development of skeletal metastasis.
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PMID:Resorbing bone stimulates tumor cell growth. A role for the host microenvironment in bone metastasis. 345 36

Alterations in c-myc proto-oncogene expression after treatment of human mammary carcinoma MDA-468 cells with epidermal growth factor (EGF) and/or transforming growth factor beta (TGF beta) have been investigated. A stimulation of c-myc messenger RNA was detected within 60 min after treatment with EGF. This induction persisted for at least 24 hr, albeit to a lower extent. The early and late increase in c-myc mRNA levels induced by EGF were inhibited by the presence of TGF beta. TGF beta alone induced little change in c-myc mRNA levels. The effect of TGF beta represents a novel action of this hormone at the level of gene expression.
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PMID:Suppression of the EGF-dependent induction of c-myc proto-oncogene expression by transforming growth factor beta in a human breast carcinoma cell line. 349 72

Modulation of epidermal growth factor (EGF) receptor expression determines cellular responsiveness to EGF and might play an important role in growth inhibition. We have investigated the actions of EGF and/or transforming growth factor type beta (TGF beta) on EGF receptor gene expression in MDA-468 human breast carcinoma cell line, which responds to EGF and/or TGF beta with growth inhibition. Using the cDNA clone pE7, which encodes 2.4 kilobases of the human EGF receptor mRNA, as a hybridization probe, we have found that exposure of MDA-468 cells to EGF results in elevated levels of EGF receptor mRNA. This increase in mRNA accumulation showed time and dose dependence. Addition of TGF beta enhances the accumulation of EGF receptor mRNA induced by EGF. Under this condition, stimulation could be detected after 1 h exposure to TGF beta with a maximum at 6-8 h. A concentration of 10 pM TGF beta gave detectable stimulation with maximal stimulation occurring at 300 pM in the presence of EGF (50 ng/ml). In contrast, TGF beta alone had no significant effect on EGF receptor mRNA accumulation. In the presence of cycloheximide, the EGF receptor mRNA was super-induced in response to EGF. Treatment of the cells with TGF beta enhances the EGF-dependent superinduction of EGF receptor mRNA produced by cycloheximide, suggesting that the stimulatory action of TGF beta does not depend on continuous protein synthesis. The results described here are consistent with the hypothesis that the growth inhibitory action of TGF beta in MDA-468 cells may be mediated, at least in part, by modulation of EGF receptor gene expression.
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PMID:Modulation of epidermal growth factor receptor gene expression by transforming growth factor-beta in a human breast carcinoma cell line. 349 59

Active phorbol esters such as TPA (12-0-tetra-decanoylphorbol-13-acetate) inhibited growth of mammary carcinoma cells (MCF-7 greater than BT-20 greater than MDA-MB-231 greater than = ZR-75-1 greater than HBL-100) with the exception of T-47-D cells presumably by interacting with the phospholipid/Ca2+-dependent protein kinase (PKC). The nonresponsive T-47-D cells exhibited the lowest PKC activity. A rapid (30 min) TPA-dependent translocation of cytosolic PKC to membranes was found in the five TPA-sensitive cell without affecting cell growth. However, TPA-treatment of more than 10 hours inhibited reversibly the growth of TPA-responsive cells. This effect coincided with the complete loss of cellular PKC activity due to the proteolysis of the translocated membrane-bound PKC holoenzyme (75K) into 60K and 50K PKC fragments. Resumption of cell growth after TPA-removal was closely related to the specific reappearance of the PKC holoenzyme activity (75K) in the TPA-responsive human mammary tumor cell lines suggesting an involvement of PKC in growth regulation.
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PMID:Protein kinase C desensitization by phorbol esters and its impact on growth of human breast cancer cells. 351 65

We have detected amplified human Ki-ras sequences in tumorigenic NIH 3T3 cells transfected with genomic DNA from the human breast carcinoma cell line MDA-MB231. Hybridization of synthetic oligonucleotides specific for human Ki-ras sequences showed a mutation at codon 13. The polymerase chain reaction with Ki-ras specific amplimers revealed a guanosine to adenosine transition at the second position of codon 13, resulting in a substitution of glycine by aspartic acid. The codon 13 mutation is also detected in one Ki-ras allele of the MDA-MB231 cell line.
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PMID:The human c-Kirsten ras gene is activated by a novel mutation in codon 13 in the breast carcinoma cell line MDA-MB231. 362 75

The growth of chemically induced mammary tumors is inhibited by both hormone manipulation as well as by retinoids. Numerous mammary carcinoma cell lines are also inhibited by retinoids. Co-treatment of estrogen receptor (ER)-positive breast cancer cells resulted in an additive effect in terms of inhibition of cellular proliferation. The addition of varying concentrations of retinoic acid (RA) to varying concentrations of tamoxifen (TMX) resulted in an additive effect on the inhibition of proliferation of the ER-positive human carcinoma cell lines (MCF-7). Co-treatment of MCF-7 cells over time with RA and TMX resulted in enhanced inhibition of growth. A similar phenomenon was observed when other synthetic retinoids were combined with TMX. This enhanced inhibition by the combination of retinoids and TMX was also observed with other ER-positive cell lines (ZR-75, T47-D), while no effect was noted on the ER-negative cell lines (MDA-MB-231, Hs578T).
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PMID:Interaction of retinoids and tamoxifen on the inhibition of human mammary carcinoma cell proliferation. 366 78

Three tumor antigens, TAG-72, carcinoembryonic antigen and a 90 Kd antigen, recognized by monoclonal antibodies (MAbs) B72.3, B1.1 and B6.2, respectively, are differentially expressed on the surface of four human breast carcinoma cell lines. These cell lines, MCF-7, BT-20, MDA-MB-231 and ZR-75-1, also expressed normal surface antigens such as the class I major histocompatibility and a second antigen found on the surface of all human cells by the binding of MAb B139. Treatment of these cells with human recombinant clone A leukocyte interferon (IFN-aA) usually resulted in an enhanced expression of the surface antigens constitutively expressed. For example, the level of B6.2 reactivity to the surface of the ZR-75-1 cells was increased more than 3-fold following IFN-aA treatment. In contrast, ZR-75-1, BT-20 and MD-MB-231 were all negative for the TAG-72 antigen both before and after IFN-aA treatment. The IFN-aA induced tumor antigen expression on the MCF-7 cell surface was shown to be time and dose dependent and consisted of a heterogeneous population of cells that exhibit clonal diversity in their response to tumor augmentation by IFN-aA. The diversity among the MCF-7 clones could not be explained by differences in the surface IFN-aA receptor.
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PMID:Recombinant human leukocyte interferon induces alterations in the antigen phenotype of human breast carcinoma cells. 375 45

Potent, structurally different tumor promoters inhibited growth of 6 human mammary carcinoma cell lines (ROOS et al, PNAS in press). This growth inhibition was investigated by measuring the phorboid receptor binding using [3H] PDBu (4 beta-phorbol 12, 13 dibutyrate). Specific, high affinity receptors were found in all six cell lines. [3H] PDBu binding affinities were higher in the cytosolic fractions than in the corresponding intact cells (K alpha = app. 1nM vs K alpha = app. 15nM). The hormone-independent cell lines (BT-20, HBL-100 and MDA-MB-231) exhibited significantly higher levels of cytosolic [3H] PDBu receptors than the hormone-dependent cells (MCF-7, T-47-D and ZR-75-1). The subcellular distribution of the [3H] PDBu binding correlated well with the distribution of the protein kinase C activity (r = 0.95).
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PMID:The cytosolic phorboid receptor correlates with hormone dependency in six mammary carcinoma cell lines. 386 78

The antineoplastic activity of the antiestrogen 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726) was determined in several estrogen-dependent mammary tumor models. The growth of the DMBA-induced rat mammary carcinoma was inhibited by doses ranging from 1 to 12 mg/kg. The maximum decrease of tumor area was 67% (control + 635%). D 16726 was also active against MNU-induced rat mammary tumors and transplanted MXT tumors of the mouse. The growth of estrogen receptor-positive MCF-7 breast cancer cells was inhibited by the hydroxy derivative D 15414 (10(-8)-10(-5) M). Because of the high binding affinity of D 15414 for the estrogen receptor (RBA 6.7-10.0) and the lack of activity against hormone-independent MDA-MB 231 breast cancer cells, a specific mode of action involving the estrogen receptor is likely.
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PMID:The inhibitory effect of 5-acetoxy-2-(4-acetoxyphenyl)-1-ethyl-3-methylindole (D 16726) on estrogen-dependent mammary tumors. 392 26

The antiproliferative effects of six different human interferons were examined on two human cell lines--HM7 (human melanoma cell line) and MDA-MB-231 (human breast carcinoma cell line). A dose-response curve was developed for each interferon in which the maximum dose applied gave at least 30% growth inhibition of control values after 96-128 h of continuous exposure. An amount of alpha-difluoromethyl ornithine (DFMO) which caused 25% growth inhibition (0.01 mM for HM7 and 0.1 mM for MDA) was added to the cultures with various doses of each interferon. The inhibitory effects of DFMO and each interferon were additive at low concentrations. In no case was a synergistic effect observed. Unlike in the murine B-16 melanoma model, we could not show a synergistic inhibitory effect between DFMO and any of the six different interferons on two human epithelial tumor cell lines.
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PMID:The in vitro interaction of alpha-difluoromethyl ornithine (DFMO) and several interferons on human cell lines. 392 26


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