Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocyte transformation by the v-myc oncogene has been used to study myelomonocytic tumor progression in vitro. Murine monocytes transformed by a recombinant retrovirus containing MC29 v-myc were found to exhibit a proliferative burst to day 28-40 post-infection. There-after growth slowed and cell number remained relatively static to day 80-90 post-infection. During both the proliferative and quiescent periods, the cells were dependent on the myelomonocytic growth factor CSF-1 for growth and viability. Analysis of this transformation revealed that the initial transformants were polyclonal, non-immortal, and non-tumorigenic in syngeneic mice. At day 80-90 post infection, a fresh round of cellular proliferation occurred and, in contrast to the initial burst, growth was sustained allowing the establishment of cell lines. These lines were found to be monoclonal, immortal, growth factor independent and, in certain cases, tumorigenic in syngeneic mice. Associated with the establishment of growth factor independent cell lines was the constitutive synthesis of the myelomonocytic growth factor, CSF-1. Proto-oncogene screening of the initial transformants and the cell lines also revealed the expression of c-raf and the CSF-1 receptor, c-fms. Our results indicate that, following transformation by v-myc, monocytes can progress in vitro to become growth factor independent and immortal and that both monocyte transformation and immortalization can be dissociated from tumorigenicity.
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PMID:Tumor progression following transformation of murine monocytes by v-myc: acquisition of immortalization and tumorigenicity. 171 Nov 91

Macrophage colony-stimulating factor (M-CSF) is a hematopoietin whose actions are essential for growth and survival of macrophages, placental development, ramification of microglia and tumor progression. The expression of the receptor for macrophage colony-stimulating factor (c-fms) is regulated by two distinct promoters: distal and proximal. The distal promoter is active in trophoblasts during embryogenesis and the proximal promoter directs expression to the cells of myeloid lineage. Here we report the generation of transgenic mice expressing beta-galactosidase under the control of the human proximal c-fms promoter and demonstrate the promoter activity in astrocytes, cells of neurological origin that partially take over the role of the macrophages in the central nervous system. Enzymatic activity of beta-galactosidase was detected in homogenated spleen, bone marrow and brain and in the cell extracts from peritoneal macrophages of transgenic mice. Immunohistochemical staining of brain showed the presence of beta-galactosidase in astrocytes. We hypothesize that M-CSF released by astrocytes, upon stimulation by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) or interleukin-1 (IL-1), regulates the expression of its own receptor.
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PMID:The promoter of macrophage colony-stimulating factor receptor is active in astrocytes. 914 89

Colony stimulating factor (CSF-1) and its receptor (CSF-1R, product of c-fms proto-oncogene) were initially implicated as essential for normal monocyte development as well as for trophoblastic implantation. However, recent findings have suggested that CSF-1 and CSF-1R might have additional roles in mammary gland development during pregnancy and lactation. Studies with osteopetrotic (op-/op-) mice, which bear a specific mutation that inactivates the CSF-1 gene, demonstrated that op-/op- mothers are incapable of normal milk production due to the incomplete development of their mammary glands during pregnancy. Also, significant increases in the levels of CSF-1 and CSF-1R proteins are observed in the epithelial cells of mammary gland during pregnancy and lactation. In vitro studies investigating the effect of the three major lactogenic hormones (prolactin, insulin, and glucocorticoids) on the expression of CSF-1 and CSF-1R have demonstrated that expression of CSF-1 can be regulated by prolactin and insulin whereas CSF-1R expression is regulated by glucocorticoids. This apparent role for CSF-1/CSF-1R in normal mammary gland development is very intriguing because this receptor/ligand pair has also been found to be important in the biology of breast cancer, where they regulate tumor cell invasion by a urokinase-dependent mechanism. This review aims to summarize recent findings on the role of CSF-1 and its receptor in normal and neoplastic mammary development which may elucidate potential relationships of growth factor-induced biological changes in the breast during pregnancy and tumor progression.
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PMID:The role of CSF-1 in normal and neoplastic breast physiology. 989 62

There is strong evidence that tyrosine kinases are involved in the regulation of cellular growth and tumor progression. Over-expressions of tyrosine kinases have been documented in a number of neoplasms. To study the roles of tyrosine kinases in colon cancer, we developed a tyrosine-kinase-expression profile for each of the four different stages of colon carcinogenesis, using normal colon mucosa, adenomatous polyps, primary carcinoma and hepatic metastases collected from the same patient. We identified 30 tyrosine kinases expressed in these tissues: they include 10 non-receptor tyrosine kinases (yes, fyn, lyn, brk, abl, arg, jak1, jak3, tyk2 and itk), 17 receptor tyrosine kinases (erbB2, PDGF-Ralpha, PDGF-Rbeta, kit, c-fms, met, ron, FGF-R1, FGF-R2, FGF-R3, FGF-R4, cek5, tie-1, tkt, axl, sky and Ins-R), 2 dual kinases (mek and sek) and one possible novel kinase. Among these kinases, arg kinase appears to be expressed at a higher level in primary carcinoma and metastatic tumor than in adjacent normal mucosa or adenomatous polyp. This result was confirmed by extensive analysis of 50 additional matched sets of normal colon and colon-tumor specimens, using arg-specific primers and RT-PCR reactions. This study identifies a possible role for arg tyrosine kinase in colon carcinogenesis, especially in the transition from adenoma to carcinoma.
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PMID:Comparative tyrosine-kinase profiles in colorectal cancers: enhanced arg expression in carcinoma as compared with adenoma and normal mucosa. 1052 89

Colony Stimulating Factor 1 (CSF-1) and its receptor, the c-fms proto-oncogene product, are expressed in normal and malignant tissues. The many actions of CSF-1 include induction of urokinase-type plasminogen activator (uPA), a serine protease involved in extracellular matrix degradation. To explore the role of CSF-1 in breast cancer progression, we evaluated the expression of CSF-1, c fms, and uPA in human breast cancer cell lines well-characterized for differing degrees of invasive, metastatic capability. The more invasive cell lines expressed elevated levels of CSF-1 by Northern analysis and ELISA. Increased uPA expression was noted in these same cell lines. CSF-1 receptor mRNA transcripts and protein were demonstrable in the different cell lines. These data suggest a role for CSF-1 in the autocrine and paracrine regulation of tumor progression in breast cancer.
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PMID:The constitutive production of colony stimulating factor 1 by invasive human breast cancer cells. 1120 75

We analyzed six cystectomized specimens diagnosed as transitional cell carcinoma by immunohistochemical evaluation to determine the presence of c-erbB2, transforming growth factor-alpha (TGF-alpha), c-myc, c-fos, and c-fms. Representative sections of flat lesions with atypia (e.g., reactive atypia, dysplasia, and carcinoma in situ) and invasive neoplasms (transitional cell carcinoma, TCC) were selected for each cystectomy specimen according to the new WHO/ISUP classification. The average percentage of cells found positive for c-erbB2 were 16.3%, 45.5%, 46.1% and 67.7% in the reactive atypia, dysplasia, carcinoma in situ, and invasive TCC, respectively. The average percentage of cells found positive for TGF-alpha were 9.7%, 13.3%, 13.5%, 30.3%, respectively. The cells were negative for the oncoproteins c-myc and c-fos. The average percentage of cells found positive for the oncoprotein c-fms was 10.6%, 15.5%, 16.7%, and 45.5% respectively. The results of this study indicated that various oncoproteins are expressed differently. c-erbB2, TGF-alpha and c-fms expression was gradually increased during tumorous progression of the urothelium from reactive atypia to invasive carcinoma. The presence of c-erbB2, TGF-alpha and c-fms is an important marker for detection of an early precursor lesions of invasive carcinoma. However, c-myc and c-fos were not expressed in the urothelial reactive atypia and dysplasia and did not correlate with tumor progression.
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PMID:Oncoprotein changes in the flat lesions with atypia and invasive neoplasms of the urinary bladder. 1129 84

Colony stimulating factor (CSF-1) and its receptor (CSF-1R, product of c-fms proto-oncogene) were initially implicated as essential for normal monocyte development as well as for trophoblastic implantation. However, studies have demonstrated that CSF-1 and CSF-1R have additional roles in mammary gland development during pregnancy and lactation. This apparent role for CSF-1/CSF-1R in normal mammary gland development is very intriguing because this receptor/ligand pair has also been found to be important in the biology of breast cancer in which abnormal expression of CSF-1 and its receptor correlates with tumor cell invasiveness and adverse clinical prognosis. Recent findings also implicate tumor-produced CSF-1 in promotion of bone metastasis in breast cancer, and a certain membrane-associated form of CSF-1 appears to induce immunity against tumors. This review aims to summarize recent findings on the role of CSF-1 and its receptor in normal and neoplastic mammary development that may elucidate potential relationships of growth factor-induced biological changes in the breast during pregnancy and tumor progression.
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PMID:The role of CSF-1 in normal physiology of mammary gland and breast cancer: an update. 1470 71

Angiogenesis is required for solid tumor growth and facilitates tumor progression and metastasis. The inhibition effects of O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), an angiogenesis inhibitor, and gemcitabine, a chemotherapeutic agent, on expression of growth factors were investigated using human pulmonary adenocarcinoma cell line, A549. The A549 cells were divided into four groups: control group, 10(-6) mg/ml gemcitabine treated group, 10(-4) mg/ml TNP-470 treated group and gemcitabine+TNP-470 treated group. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and its receptors, FMS-like tyrosine kinase-1 (FLT-1) and kinase insert domain-containing receptor (KDR), in different groups were measured. The growth of A549 cell cultured with gemcitabine or TNP-470 was inhibited in an almost dose-dependent manner. Although gemcitabine (10(-6) mg/ml) alone and TNP-470 (10(-4) mg/ml) alone had no effect on the mRNA and protein expression of VEGF and its receptors (FLT-1, KDR) in A549 cells compared to the control (P>0.05), 10(-6) mg/ml gemcitabine in combination with 10(-4) mg/ml TNP-470 had significant effect (P<0.01). Moreover, combination of the two drugs significantly inhibited the mRNA expression of VEGF, FLT-1 and KDR compared to either drug alone (P<0.05). This study suggests that combined treatment with TNP-470 plus gemcitabine may augment the antiangiogenic and antineoplastic effects in lung cancer cells in vitro.
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PMID:Inhibition of expression of vascular endothelial growth factor and its receptors in pulmonary adenocarcinoma cell by TNP-470 in combination with gemcitabine. 1697 27

Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor that targets both angiogenic pathways (i.e., vascular endothelial growth factor receptor and platelet-derived growth factor receptor) and direct pro-oncogenic pathways (e.g., stem-cell factor receptor and FMS-like tyrosine kinase-3). Preclinical studies with this agent have indicated that it exhibits robust inhibitory activity against these targets. Clinical trial results have demonstrated the therapeutic potential of this agent and have implicated sunitinib targets in the pathophysiology of malignancies such as renal cell carcinoma and gastrointestinal stromal tumour. This paper reviews the preclinical data supporting the development of this agent and its translation from benchtop to bedside. It also highlights the importance of the multiple pathways that may be involved in cancer progression and the importance of these pathways in selected malignancies.
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PMID:A preclinical review of sunitinib, a multitargeted receptor tyrosine kinase inhibitor with anti-angiogenic and antitumour activities. 1776 21

Circulating heat shock protein (HSP)-27 is associated with tumor progression and increased post-injury infection. Extracellular HSP-27 might alter monocyte (MO)-derived DC and/or MPhi function to mediate immunosuppression. HSP-27 treatment inhibited expression of CD1a and CD1b/c, antigen uptake, and allogeneic T cell induction (MLR) by IL-4 + GM-CSF-differentiated human DC while increasing some MPhi characteristics ( upward arrowCD14, upward arrowCD16, upward arrowCD163). MO cytokine receptor profiles elicited by 24-h exogenous HSP-27 treatment remained supportive of immature DC (iDC) emergence ( upward arrowIL-4R, downward arrowIL-6R, downward arrowM-CSFR). IL-10, IL-6, and M-CSF (which promote MPhi differentiation) were significantly increased in IL-4 + GM-CSF + HSP-27 MO-->iDC differentiation cultures. However, HSP-27 treatment during MO differentiation to DC increased programmed cell death ligand 1 coinhibitor and depressed CD86 costimulator expression in parallel to decreased iDC MLR activity. This suggested that increased MPhi differentiation was not solely responsible for HSP-27 reduction of differentiating DC activity. HSP-27 treatment actually depressed the phagocytic capacity of MO differentiated to MPhi by IL-10 or M-CSF culture. CD163 (hemoglobin receptor) expression was depressed on M-CSF + HSP-27 MO-derived MPhi. HSP-27-mediated inhibition of MO-->iDC differentiation was reversed by p38alpha & beta inhibitor (SB202190) addition or TLR4 receptor modulation. HSP-27 impaired appropriate MO-->iDC and MO-->MPhi differentiation modulating expression of receptors necessary for their proper functions. This suggests that endogenous HSP-27 has immunoregulatory activities which could contribute to immunopathology.
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PMID:Exogenous heat shock protein 27 uniquely blocks differentiation of monocytes to dendritic cells. 1782 91


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