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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased number of interphasic nucleolar organizer regions containing ribosomal cistrons associated with argyrophilic proteins (AgNORs) has been described in human malignant tumor cells. In this study variations in AgNOR numbers have been compared with changes of cell kinetics, evaluated by the mitotic count (MC) and bromodeoxyuridine labeling index (BrdU LI), during gastric carcinogenesis induced with N-methyl-N'-nitro-N-nitrosoguanidine (NG) in rats. Significant differences (2 P < 0.005) in AgNOR mean numbers, evaluated in the antral isthmic cells, in MC mean values and BrdU LI, evaluated in the whole antral cellular population, were found when comparing areas of acute gastritis, atrophy and hyperplasia in NG-treated rats with the normal mucosa in controls. No differences were observed in MC and BrdU LI between normal antrum and carcinoma cells which showed an AgNORs mean number lower than in the isthmic cells of controls (2 P < 0.005). Moreover, significant correlations were found comparing changes in AgNOR numbers with MC (r = 0.89, P < 0.001) and BrdU LI (r = 0.66, P < 0.001) in different lesions. These data show that evaluation of AgNOR numbers does not allow the identification of malignant cells in NG-induced gastric carcinoma. However AgNOR quantification seems to be a reliable index of cell kinetics and related well with the cellular dividing fraction.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Interphasic nucleolar organizer regions expression and cell kinetics evaluation during gastric carcinogenesis induced by nitrosoguanidine in the rat. 135 3

The influence of estrogen on mammary carcinogenesis was studied in female Sprague-Dawley rats ovariectomized at the age of 36 days and given injections of 17 beta-estradiol (group I:0, II:1, III:10, IV:100, V:1000 micrograms/2 days) between the ages of 36 and 250 days and a single oral dose of 20 mg of 7,12-dimethylbenz(a)anthracene (DMBA) at the age of 50 days. No palpable mammary carcinomas were detected up to the age of 135 days. At the age of 135 days, each group was divided into two subgroups (a and b). Rats of the second subgroup (Ib, IIb, IIIb, IVb and Vb) were given additional injections of progesterone (P; 4 mg/2 days) between the ages of 135 and 250 days. At the age of 250 days, the incidence of mammary carcinoma was significantly higher in rats from group IIIb than in groups Ib and IIIa, and that in group IVa was also higher than in group Ia. The incidence in group IVb was significantly lower than in group IVa. The carcinomas in group IIIb were palpable papillo-tubular adenocarcinomas and those in group IVa were secretory micro-adenocarcinomas. These results indicate that the induction of mammary carcinomas by DMBA is totally inhibited by ovariectomy and/or high doses of estrogen, but that mammary carcinomas are initiated by DMBA under hormonal conditions in which suitable levels of estrogen are present. They also suggest that the growth of DMBA-induced mammary carcinomas in the rats from group III were accelerated by additional injections of P and that those in rats from group IV were inhibited by additional P.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Influence of estrogen and progesterone on the induction of mammary carcinomas by 7,12-dimethylbenz(a)anthracene in ovariectomized rats. 136 Jul 23

The use of backscattered electron imaging (BEI) as a routine procedure for examining autoradiographic reactions in scanning electron microscopy (SEM) is described. This technique allows the determination of the number of receptor sites occupied by 125I-epidermal growth factor (EGF) on whole cells. The effect of 1.25 dihydroxyvitamin D3 (1,25 (OH)2D3) on the number of epidermal growth factor receptors (EGF-R) in the BT 20 human mammary carcinoma cell line (which is known to possess a very high number of EGF-R) has been evaluated with this method. To compare the silver grain density over the cells (controls and 1,25 (OH)2D3-treated cells) we used an image analysis system Quantimet 900. The results were compared with those of a previous study using transmission electron microscopy (TEM). This study confirmed the results obtained with TEM and showed the even distribution of receptors sites on a single cell and a large difference in the number of receptor sites from one cell to another. The use of BEI to visualize the autoradiographic reaction in SEM allowed the examination of a large surface with good contrast and resolution and eliminated artefacts not corresponding to the silver grains. It gave new information not delivered by quantitative TEM autoradiography and was easier and faster to use. The efficient use of SEM autoradiography combined with BEI could facilitate whole area distribution mapping of radioactive labeling.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Visualization and rapid quantification of autoradiographic labeling in scanning electron microscopy applied to localization of receptor sites on the surface of whole cells. 136 Jul 25

Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKC gamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKC gamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC.
Mol Pharmacol 1992 Dec
PMID:Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin. 136 42

In order to elucidate the mechanism of androgen-regulation of genes expressed only in the prostate gland, the effects of steroid hormones on the biosynthesis and secretion of human prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were studied in the human prostatic carcinoma cell line, LNCaP. This cell line produces PAP and PSA, both of which were found to be similar to the proteins purified from and located in human prostatic tissue, as shown by Western blot analysis. The synthetic androgen, R1881, regulated the biosynthesis of these two important tumour marker proteins inversely: the amount of PSA released into the medium was increased to 506% +/- 100 of the control levels, while that of PAP was decreased to 26% +/- 3, in 7 days. These effects were dependent on the concentration of the steroid in the growth medium. The androgen-dependent changes observed in the amounts of the secreted proteins were correlated with alterations in their intra-cellular levels. LNCaP cells were found to have very different capacities for secreting PAP and PSA. Whereas the measurable, cellular amounts of PSA and PAP were of similar magnitudes, much larger amounts of PSA than PAP were secreted into the medium. PSA was also found to be more stable than PAP in the culture medium of the LNCaP cells. Other steroids could elicit effects on PAP and PSA biosynthesis similar to those induced by R1881, and the combined effects of effective concentrations of these steroids were undistinguishable from those caused by each one of them separately, suggesting that all these compounds compete for binding to the same modified androgen receptors of the LNCaP cells. Thus, our results confirm the observations of the altered nature of the LNCaP androgen receptors, and demonstrate the ability of these ligands to produce changes in the expression of androgen-dependent prostatic genes. The fact that the changes observed at the protein level were accompanied by increased levels of PSA mRNAs and by decreased levels of PAP mRNA in steroid-treated cells, suggests that one of the targets of androgen and steroid action in the regulation of these genes is at the mRNA level.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Steroids inversely affect the biosynthesis and secretion of human prostatic acid phosphatase and prostate-specific antigen in the LNCaP cell line. 137 97

Human CG is composed of two subunits, alpha and beta. In addition to its eutopic synthesis in normal and malignant trophoblasts, the hormone is produced ectopically by a variety of tumor cell lines of nonplacental origin. Regulation of the alpha CG gene in trophoblasts appears to differ from that in nontrophoblasts. To determine whether these differences are reflected in the chromatin structure at the alpha CG locus, DNase I-hypersensitive sites within this domain were mapped in human tumor cell lines that differentially express the gene. Two hypersensitive sites were detected in DNA from cell lines that produce the alpha-subunit. The latter includes trophoblastic (JAr and JEG-3 choriocarcinoma) and nontrophoblastic (HeLa cervical carcinoma and ChaGo bronchogenic carcinoma) tumor cell lines. The most prominent site (HS 1) was located approximately 100 base pairs upstream from the transcription start site. In trophoblasts, accessibility of HS 1 increased substantially upon induction of the gene by cAMP, likely reflecting alterations in DNA-protein interactions at the cAMP response element and/or tissue-specific enhancer. In nontrophoblasts, where alpha-subunit synthesis is enhanced by sodium butyrate but not by cAMP, neither butyrate nor cAMP altered the accessibility of HS 1. The HS 2 is comprised of multiple sites with weak to moderate DNase sensitivity located downstream at +1600 to +4000 in cell lines that produce alpha-subunit. Cell lines that do not express the alpha CG gene possess a distinct hypersensitive site (HS 3) within the first intron at about +600; these include 3A-Sub-E (SV40 transformed placenta), CBT (glioblastoma multiforme), and CaSki (cervical carcinoma). Cleavage by DNase at HS 1 and HS 2 is not evident in nuclei from cell lines that do not produce alpha-subunit. These results suggest that HS 1 and HS 3 are characteristic of active and inactive states of the alpha CG gene, respectively, and that the accessibility of HS 1 generally correlates with the level of expression.
Mol Endocrinol 1992 May
PMID:Deoxyribonuclease-hypersensitive sites in the glycoprotein hormone alpha-subunit gene from trophoblastic and nontrophoblastic human tumor cell lines: correlation with expression and effect of chemical inducers. 137 9

Bleomycin hydrolase (BH) is a cysteine proteinase that terminates the pharmacological action of bleomycin (BLM). Amino acid sequence data obtained from a tryptic digest fragment of purified rabbit lung BH were used to synthesize a 14-amino acid peptide (LAVLEQEPIVLPAK; BHP14), which was conjugated to horseshoe crab hemocyanin and used to produce rabbit antiserum that was immunoreactive to both BHP14 and rabbit BH. Anti-BHP14 binding to BHP14 could be competitively blocked by the presence of either BHP14 or BH. Anti-BHP14 recognized both purified rabbit liver BH and postmicrosomal fraction from rabbit liver on Western blot, as a single band of M(r) approximately 48,000. Anti-BHP14 inhibited, in a concentration-dependent manner, BH activity in rabbit liver cytosolic fractions, as measured by deamido-BLM A2 formation. Thus, we have generated an epitope-specific neutralizing antibody to rabbit BH, which can block the metabolism of BLM by homogenates from rabbit tissue. These results suggest that the LAVLEQEPIVLPA epitope of rabbit BH is involved in the metabolism of BLM or is topologically near the active site. Furthermore, a BLM-resistant squamous carcinoma (C-10E) exhibited slightly more immunoreactivity, by enzyme-linked immunosorbent assay, to anti-BHP14 than did the parental A-253 cells, and a partially revertant (C-10E ND) cell line had intermediate anti-BHP14 binding. BH activity in these cell lines was in the same rank order as antibody binding, but differences in immunoreactivity were less than differences in enzymatic activity. Our epitope-specific neutralizing antibody should be useful in the further characterization of BH.
Mol Pharmacol 1992 Jul
PMID:Neutralization of bleomycin hydrolase by an epitope-specific antibody. 137 25

In normal epidermis, the expression of keratins 1 and 10 is associated with the loss of proliferative capacity and the onset of terminal differentiation. Keratins 1 (K1) and 10 (K10) are commonly expressed in the differentiating layer of benign tumors, but are lost during progression from the benign to the malignant state in skin carcinogenesis. Active gene constructs of mouse K1 and K10 were introduced into papilloma and carcinoma cell lines derived from keratinocytes to analyze the consequences of the expression of these keratins on the organization of the endogenous cytoskeletal network and on the mitotic activity of the recipient cells. Exogenous K1 integrated into the preexisting keratin K5/K14 network of both SLC-1 carcinoma and 308 papilloma cells. The formation of a recombinant cytoskeleton was more restricted for K10 than for K1 and appeared to be related to a requirement for cessation of cell division before K10 could integrate. The integration of exogenous K1 filaments into the endogenous keratin network was compatible with sustained proliferation of SLC-1 carcinoma cells in vitro. However, the exogenous gene was not expressed in tumor grafts in vivo. In contrast, stable K1 or K10 transfectants could not be selected in 308 cells, suggesting that benign tumor cells expressing suprabasal keratins cannot sustain proliferation.
Mol Carcinog 1992
PMID:Relationship between the expression of differentiation-specific keratins 1 and 10 and cell proliferation in epidermal tumors. 138 Feb 47

In the present study the establishment and characterization of a new oxyphilic papillary thyroid carcinoma cell line--ONCO-DG1- is given. With immunohistological, histochemical and flow cytometric methods, ONCO-DG 1 cells revealed features of epithelial differentiation. Furthermore the cells formed von Kossa-positive deposits resembling psammoma bodies in monolayer and spheroid culture until late passages. The tumor cell line is now in the 40th subculture. Because of the ability to form multicellular tumor spheroids (MCTS), this cell line is a good model for examining the interaction between thyroid tumor cells and confluent human endothelial cells on extracellular matrix in vitro. It is also suitable for xenotransplantation studies, because it is tumorigenic in NMRI nude mice in vivo.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Establishment and characterization of a human papillary thyroid carcinoma cell line with oxyphilic differentiation (ONCO-DG 1). 138 Nov 31

Keratins have been demonstrated to be suitable markers of changes taking place during epithelial neoplasia. Therefore, we analyzed 18 mouse skin tumors (nine papillomas and nine squamous cell carcinomas), induced either by two-stage carcinogenesis with 7,12-dimethylbenz[a]anthracene(DMBA)/12-O-tetradecanoylphorbol-13-acetat e or complete carcinogenesis with DMBA, by immunofluorescence with a monoclonal antibody to keratin (K) 8 (TROMA-1). Immunoperoxidase staining and immunoblotting were also used on selected tumor samples to further explore for the presence of K8. All of the papillomas tested were negative for the presence of K8, whereas the carcinomas were positive. The level of K8 expression in carcinomas showed a positive correlation with the degree of malignancy. Northern blot analysis using a K8 cDNA probe suggested that control of K8 expression in mouse skin tumors occurs at the transcriptional level. Double-label immunofluorescence staining using TROMA-1 and RK13 antibodies demonstrated that K8 did not generally colocalize with K13, a keratin normally found in internal stratified epithelial but aberrantly expressed in mouse epidermal tumors. Furthermore, tumors expressing high levels of K8 showed a reduced expression of K13. Histological examination of immunoperoxidase-stained tumors demonstrated that K8-positive cells were mainly found in anaplastic areas, whereas K13 foci were restricted to well-differentiated regions. Our results demonstrate that K8 expression is a marker of late stages of carcinoma progression in the mouse skin carcinogenesis model.
Mol Carcinog 1992
PMID:Aberrant expression of the simple epithelial type II keratin 8 by mouse skin carcinomas but not papillomas. 138 41


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