Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Rice-500 Leydig cell tumor of Fischer rats is associated with humoral hypercalcemia in vivo and produces a factor that stimulates cAMP formation in cultured rat osteosarcoma cells. We found that cultured human skin fibroblasts respond to both human PTH-(1-34) and the factor produced by cultured rat Leydig tumor cells with a dose-dependent rise in cAMP formation. The time courses for stimulation of the two agents were similar, and stimulation by both was blocked by the competitive PTH antagonist [8,18-norleucine,34-tyrosine]bovine PTH-(3-34) amide. These data suggest that PTH-like factors secreted by a murine tumor are capable of interacting with the human PTH receptor.
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PMID:A factor produced by cultured rat Leydig tumor (Rice 500) cells associated with humoral hypercalcemia stimulates adenosine 3',5'-monophosphate production via the parathyroid hormone receptor in human skin fibroblasts. 298 87

We have purified peptides with PTH-like bioactivity from a rat Leydig cell tumor (H-500) and a human squamous cell carcinoma, both associated with a syndrome of humor-induced hypercalcemia. Tumor extracts were shown to be active in an in vitro renal cytochemical bioassay and in an in vitro osteosarcoma cell (UMR 108) adenylate cyclase assay; activity in both assays could be reduced by the PTH antagonist [norleucine-8,18,tyrosine-34]bovine PTH-(3-34)-amide. Partially purified extracts of both tumors and of rat tumor-conditioned culture medium were active in vivo in thyroparathyroidectomized rats in preventing hypocalcemia and increasing fractional phosphorus excretion and cAMP excretion. Ion exchange chromatography demonstrated that active peptides were basic in character. Employing reverse phase HPLC and gel permeation HPLC, active peptides of approximately 9,000 and 9,500 daltons were purified from extracts of the human and rat tumors, respectively, which had similar but not identical compositions. Two additional bioactive peptides were detected in rat tumor extract, and the more active had a mol wt of approximately 28,000. The results demonstrate that peptides that mimic PTH in a variety of in vivo and in vitro bioassays can be extracted from malignancies associated with hypercalcemia, that multiple molecular species may be detected in tumors that demonstrate PTH-like activity, and that at least one of these peptides may be similar in two tumors of highly divergent cell and species origin.
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PMID:Purification of peptides with parathyroid hormone-like bioactivity from human and rat malignancies associated with hypercalcemia. 394 72

PTH-related peptide (PTHrP) has been shown to be the major mediator of hypercalcemia of malignancy, but may also exert effects on cell growth and differentiation. The Leydig cell tumor H-500, when implanted in Fischer rats, produces abundant PTHrP and eventually causes the death of the host animal. In the present study we have used antisense RNA technology to block the effects of PTHrP in H-500 Leydig tumor cells in vivo. The full-length rat PTHrP complementary DNA encoding amino acid -36-->141 was subcloned as an EcoRI-BglII insert in the antisense orientation into the mammalian expression vector pRc/CMV to produce the plasmid pRc-PAS. This plasmid was then stably transfected into the H-500 Leydig tumor cells with a Lipofectin reagent. After selection with the neomycin derivative G-418, a stable cell line, H-500-PTHrP-AS, was obtained which showed 80% inhibition of endogenous PTHrP messenger RNA compared to wild-type or vector-only transfected H-500 cells. Conditioned culture medium from these experimental cells showed a marked decrease in PTHrP immunoreactivity and in the ability of the medium to stimulate adenylate cyclase in UMR-106 rat osteosarcoma cells. Furthermore, inhibition of PTHrP production resulted in a significant increase in the doubling time of the H-500 cells. Transfection of the experimental plasmid into Rat-2 fibroblasts, which do not produce PTHrP, had no effect on cell growth. Control and experimental cells were then implanted sc into male Fischer rats. Animals were killed at timed intervals, and their tumor volumes were determined. Experimental animals receiving cells transfected with antisense PTHrP plasmid showed near-normal levels of plasma calcium and decreased expression of tumoral PTHrP messenger RNA. These animals also showed a 30-70% lower tumor volume during the course of the experiment compared to control animals. These studies have demonstrated that PTHrP can play a role as a promoter of tumor growth in vitro and in vivo.
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PMID:Regulation in vivo of the growth of Leydig cell tumors by antisense ribonucleic acid for parathyroid hormone-related peptide. 758 90

Mxi1, a member of the Myc family of transcription factors, negatively regulates Myc oncoprotein activity and thus may be a tumor suppressor gene. It is mutated in a few human prostate cancers. Rat Mxi1 was isolated as a selective overexpressive message in rat esophageal cancer induced by N-nitrososarcosine ethyl ester using differential display and polymerase chain reaction cloning. Reverse transcription, single-strand conformation polymorphism analysis and subsequent DNA sequencing were used to screen mutations for the rat Mxi1 coding region including the functional domains, Sin3-interacting, helix-loop-helix and leucine zipper in samples from 24 rat tumor tissues and various cell lines. Seven mutations were revealed to exist in six rat tumors (including two esophageal tumors and a breast cancer), and three rat tumor cell lines: Leydig cell tumor, osteogenic sarcoma, and pituitary tumor. No coding changes were detected in 34 samples of human sporadic gastric adenocarcinoma. A silent base substitution (GAG to GAA) at codon 131 was also identified in six rat tumors as well as in one human gastric cancer. Our results indicate that Mxi1 is often mutated in experimental rat tumors but mutations are rare in human sporadic cancers. The Mxi1 tumor suppressor gene may be a cellular target of strong carcinogens. Considering the frequency of mutations in chemical carcinogen-induced tumors, searches for Mxi1 mutation in human tumors should be directed toward patients with a specific epidemiological background.
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PMID:Mxi1 is a potential cellular target of carcinogens and frequently mutated in experimental rat tumors and tumor cell lines. 1084 26