摘要:

AbstractPrevious results have shown that tumor promoters modify the properties of the epidermal growth factor (EGF) receptor through the activation of protein kinase C. Diacylglycerol‐generating factors such as platelet‐derived growth factor (PDGF) and p28sisshould activate protein kinase C and alter EGF receptor properties in a similar manner. To test directly the involvement of protein kinase C in the action of media from v‐sis‐transformed cells on the EGF receptor, Swiss 3T3 cells were first extensively treated with various concentrations of the tumor‐promoter phorbol dibutyrate (PDBu) This treatment reduced levels of active protein kinase C in the cells, making them less responsive to subsequent rechallenge with the tumor promoter. The results demonstrate that there are at least two components to the action of media from v‐sistransformed cells on EGF binding: a labile factor that confers protein kinase C independence and a stable factor that appears to be dependent on protein kinase C. The action of the first factor cannot be mimicked by transforming growth factor‐β or EGF in either the presence or absence of PDGF. The action of the second factor is similar to that of PDGF. These findings indicate that heterologous regulation of the EGF receptor can occur through both protein kinase C‐dependent and ‐in

ISSN:0730-2312    

DOI:10.1002/jcb.240340102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractFrom the mouse JB6 epidermal cell line C122 we have isolated a cDNA clone representing a 1.6‐kilobase mRNA, called 2ar, that exhibits a biphasic induction in response to 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). The first phase of induction in subconfluent cells is transient, peaking at 6 h after the addition of TPA and returning to noninduced levels by 24 h. When the cells reach plateau density, in the continued presence of TPA, this mRNA is reinduced and remains so upon continued exposure to the tumor promoter. Serum and certain growth factors also induce 2ar mRNA in serum‐deprived quiescent fibroblasts. In vitro nuclear “run‐on” transcription experiments indicate that the induction of 2ar mRNA is controlled at the tr

ISSN:0730-2312    

DOI:10.1002/jcb.240340103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractSomatic cell hybrids were isolated from fusions of diploid embryonic rat fibro‐blasts with transformed Rat‐1 cells which contained 4 to 5 copies of the transforming human Ha‐ras 1 gene. In contrast to their transformed parental cells four hybrid clones showed normal morphology, long latency periods of tumorigenicity in newborn rats, anchorage requirement of proliferation, and an eightfold‐reduced amount of secreted transforming growth factor activity. Thus these hybrids are called suppressed with regard to expression of the Ha‐ras‐induced transformed phenotype. Tumorigenic derivatives of the suppressed hybrids that had segregated chromosomes were isolated. Since two of the tumorigenic hybrid clones showed the similar low level of secreted transforming growth factors as the suppressed hybrids, decreased production of transforming growth factor activity is unlikely to be a sufficient criterion for suppression of malignancy. Whereas one of the suppressed hybrids expressed the transforming gene product p21 at a level similar to that of the transformed parental cells, other suppressed hybrids expressed less p21. This suggests that the suppressed phenotype can be regulated at the posttranslational level of p21 but that additional controls of expression of p21 are likely to exist. DNA of the suppressed hybrids transformed Rat‐1 cells to proliferation in the presence of semisolid agar. Thus the activated human Ha‐ras gene in the suppressed hybrids retained its biological activity even though it did not transform these cells to

ISSN:0730-2312    

DOI:10.1002/jcb.240340104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe transcriptional activity of ten cellular oncogenes was analyzed in somatic cell hybrids that had been obtained after fusion of tumorigenic Chinese hamster cells and normal mouse fibroblasts. The hybrids showed either the tumorigenic or the nontumorigenic phenotype (suppression of tumorigenicity). Out of ten c‐one genes analyzed, four (c‐Ha‐ras, c‐Ki‐ras, c‐myc, and c‐fos) were found to be transcriptionally active at similar levels in tumorigenic as well as in nontumorigenic (suppressed) hybrids. Thus we conclude that suppression of tumorigenicity in Chinese hamster × mouse somatic cell hybrids does not correlate with quantitative changes in expression of these cellular oncogenes. The remaining six cellular oncogenes (c‐abl, c‐erb A and B, c‐fes, c‐myb, and c‐sis) were not transcriptionally

ISSN:0730-2312    

DOI:10.1002/jcb.240340105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractWEHI‐274 is a monocytic leukemia that arose in a BALB/c mouse infected with Abelson murine leukemia virus. A series of subclones were derived from early passages of this tumor. Three subsets of these leukemogenic subclones were identified. Two subsets demonstrated autostimulatory patterns of growth. This was due to the ectopic production of the T‐cell lymphokine the panspecific hemopoietin IL‐3 in one case and of the T‐cell lymphokine granulocyte‐macro‐phage colony‐stimulating factor (GM‐CSF) in the other. The third type of subclone did not secrete any autostimulatory growth factor. In the subclone producing IL‐3, one copy of IL‐3 gene was rearranged and abnormal IL‐3 RNA transcripts were present in the nucleus. Subclones producing GM‐CSF also contained abnormal GM‐CSF RNA transcripts, although no rearrangement of the GM‐CSF gene was detected. All three sets of subclones shared a common rearrangement of one c‐myboncogene, suggesting that they share a common ancestor. These results suggest that initiation or progression of leukemogenic behavior in this abnormal clone occurred in three different ways, two of which involved autostimulation by the ectopic activati

ISSN:0730-2312    

DOI:10.1002/jcb.240340106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractInterleukin 2 (IL 2) is a polypeptide growth factor essential for the proliferation and differentiation of T lymphocytes, large granulocytic lymphocytes, and, potentially, cells of the antibody‐producing lineage, B lymphocytes. Many of the biological properties of IL 2 may be mimicked or potentiated by a potent class of tumor promoters, phorbol esters. Phorbol esters have recently been shown to associate with and activate a unique phospholipid/Ca2+‐dependent phosphotransferase, protein kinase C (PK‐C). Utilizing two‐dimensional gel electrophoresis, we have compared the IL 2 and diacylglycerol‐induced protein phosphorylation patterns of several IL 2‐dependent murine cell lines. Both IL 2 and synthetic diacylglycerol, 1‐oleyl‐2‐acetyIglycerol (OAG), stimulated phosphorylation of a number of protein substrates in intact cells compared to unstimulated controls. Three groups of substrates were identified; the first showed increased phosphorylation following stimulation with either IL 2 or OAG, while the second and third groups showed increased phosphorylation following stimulation with IL 2 but not OAG, and with OAG but not IL 2, respectively. Here, we characterize the kinetics of phosphorylation of one cellular substrate, p68, which appears to be phosphorylated in response to direct activators of PK‐C or lymphoid or myeloid growth factors in their respective lineage cell lines. The observation that IL 2 also stimulates a unique series of phosphoproteins in addition to those induced by direct PK‐C activators suggests that IL 2 may initiate additional protein kinase activities, unrelated to PK‐C, which may also be critical for the ligand‐receptor signal transduction process regulating g

ISSN:0730-2312    

DOI:10.1002/jcb.240340107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractActivities of angiotensin‐converting enzyme (ACE), other proteinases, and eosinophil chemotactic factor (ECF‐G) are known to be elevated in hepatic hypersensitivity granulomas of thymus intact (nu/+) mice afterSchistosoma mansoniinfection. The enzyme activities also increase, but to a lesser degree in hepatic granulomas of athymic nude (nu/nu) mice, and ECF‐G is not detectable. In this study isolated hepatic granulomas from nu/+ mice were grafted into the skin of uninfected nu/nu mice, and changes in those cellular functions were determined to examine whether the newly formed granulomas by recipient nu/nu cells acquire the functional activities as well as the histological appearance of nu/+ granulomas. ACE and ECF‐G rapidly disappeared from grafted sites during the first 5 days, corresponding to loss of nu/+ cells from the graft. Reduction in activities of arylsulfatases, lysozyme, and acid phosphatase also occurred, but to a lesser extent. Recovery of ACE and ECF‐G activities to the levels seen in nu/+ hepatic granulomas was observed by 14 days after grafting when nu/nu cells had accumulated in the grafts and formed new granulomas. Other enzymes increased to approximately half the levels seen in grafted donor granulomas. Circulating eosinophilia also increased. The findings indicate that nu/nu cells that accumulated in the skin grafts not only morphologically mimicked nu/+ type granulomas but also demonstrated nu/+ levels of cellular function. Analysis of skin granulomas developing in nu/+ mice after grafting of nu/+ hepatic granulomas showed the similar histology and enzymatic changes, whereas the skin sites inoculated with purified schistosome eggs alone caused neither significant histological changes nor elevation of ACE

ISSN:0730-2312    

DOI:10.1002/jcb.240340108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

ISSN:0730-2312    

DOI:10.1002/jcb.240340101

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY