Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on 10 human lung carcinoma cell lines were compared to those seen on normal human bronchial epithelial (NHBE) cells. TPA (0.1 to 100 nM) did not enhance the clonal growth rate for any of the cell lines. As little as 3 nM TPA induced the NHBE cells to undergo terminal squamous differentiation and thus completely inhibited their proliferation; in contrast, none of the carcinoma cell lines was significantly inhibited at this concentration, and they all continued to proliferate in as much as 100 nM TPA. To determine if this lack of TPA inhibition of clonal growth reflected resistance to TPA induction of terminal squamous differentiation, we measured the ability of TPA to induce cross-linked envelope formation and to increase plasminogen activator activity in four carcinoma cell lines. Cross-linked envelopes were not induced in two lines, and only a small number were induced in the other two lines relative to NHBE cells; plasminogen activator activity was induced in NHBE cells but not in any of the cell lines.
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PMID:Differential effects of 12-O-tetradecanoylphorbol-13-acetate on cultured normal and neoplastic human bronchial epithelial cells. 648 72

A 66-year-old man with metastatic prostatic carcinoma treated with high-dose (5 mg) diethylstilbestrol therapy underwent orchiectomy to allow discontinuation of estrogen. An extensive ecchymosis developed postoperatively in an area covered by elastic dressing tape; subsequently, it was learned that the patient had a recent history of frequent ecchymoses with mild trauma that proceeded to vesiculation. His alpha2-antiplasmin level was 132 percent, fibrin split products 4 micrograms/ml, and fibrinogen 293 mg/dl; routine coagulation results were normal. However, the level of releasable vascular plasminogen activator in a specimen drawn prior to surgery was 3.6 CTA units/ml, the highest value ever reported in this laboratory.
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PMID:Increased releasable vascular plasminogen activator and a bleeding diathesis. 654 Sep 87

Line 10 guinea pig carcinoma cells cultured in serum-free medium for 4 hr elaborate plasminogen activator (PA) activity that remained in the supernatant after ultracentrifugation (100,000 X g, 90 min). PA activity in line 10 conditioned medium occurred in both active and cryptic forms. The vast majority of active PA adsorbed to lysine-Sepharose and could be eluted at low pH as several activities that electrophoresed in the Mr 50,000 to 80,000 range on nonreduced sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A small amount of active PA, running in the Mr 50,000 to 60,000 region, and cryptic PA did not adhere to lysine-Sepharose. Treatment of lysine-Sepharose-nonadherent fractions with catalytic amounts of plasmin or trypsin induced substantial new PA activity that adsorbed to lysine-Sepharose, bound [3H]diisopropylfluorophosphate, and that electrophoresed as several bands of activity with molecular weights from 50,000 to greater than 100,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Of additional interest, the amount of active PA measured in conditioned medium was substantially increased when certain protease inhibitors, tranexamic acid, epsilon-aminocaproic acid, or Trasylol, were included during culture.
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PMID:Cryptic and active plasminogen activators secreted by line 10 tumor cells in culture. 668 8

The plasminogen activator levels of a series of murine tumors commonly used in cancer drug screening were determined and compared to the levels found in normal mouse tissues. Tumors high in plasminogen activator included the B16 and colon 26. The Lewis lung and M5076 carcinoma showed an intermediate level of activity, while the plasminogen activator activity in the L1210 leukemia and colon 38 was barely elevated above background. The specific activity of the enzyme (per micrograms protein) in extracts of B16 and colon 26 was three or four times higher than in the most active normal organs surveyed (kidney, lung, brain and intestine). The high level of plasminogen activator activity measured in extracts of the B16 tumor was reflected in a substantial elevation of the levels of fibrin degradation products in the serum of mice carrying this tumor. This result suggests that the tumor-associated plasminogen activator activity is less subject to inhibitory controls in vivo than is the plasminogen activator of most normal tissues, since the total mass of the tumor was far less than the total mass of the fibrinolytically active tissues, and yet the bulk of the fibrin degradation products were caused by the tumor. We conclude that the high levels of plasminogen activator activity which are observed in many human tumors are found only in some of the transplantable murine tumors. Since this enzyme is active at an increased level in vivo in mice carrying the B16 tumor, plasminogen activator may be a suitable target for selective, enzyme-activated chemotherapy with this tumor test system.
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PMID:Plasminogen activator in normal and tumor-bearing mice. 668 48

Multiple molecular forms of plasminogen activator were detected in normal human mammary epithelial cells in culture. Cells derived from (normal) breast mammoplasty specimens and grown on the surface of collagen gels exhibited three major classes of plasminogen activator isozymes (Mr = 100,000 [100K], 75,000 [75K], and 55,000 [55K]). The activity of the 100K and 75K isozymes was greatly reduced when the cells were grown on conventional tissue-culture-grade plastic surfaces. MCF-7, a human mammary carcinoma cell line, exhibited predominantly or exclusively the 55K isozyme, irrespective of the cell growth substratum. The activity of the 55K isozyme was more than twofold higher for MCF-7 cells grown on collagen gels than for cells grown on plastic. Progesterone, diethylstilbestrol, and estrogen stimulated the activity of the 55K isozyme of MCF-7 cells, but only when the cells were grown on a plastic surface. The plasminogen activator activities of the normal human mammary epithelial cells were not stimulated by these hormones, irrespective of the growth substratum. These results show that the expression of plasminogen activator isozymes by human mammary epithelial cells is subject to modulation by the extracellular matrix. Normal and malignant cells may differ in their responsiveness to these effects.
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PMID:Effect of the extracellular matrix on plasminogen activator isozyme activities of human mammary epithelial cells in culture. 668 79

We report the isolation of six cell lines (designated EB cell lines) from cultures of the hypoxanthine guanine phosphoribosyl transferase-deficient (HGPRT-) feeder-dependent embryonal carcinoma cell line PSA4TG12 which have undergone in vitro differentiation, and of clonal derivatives of these lines. Whereas some lines possess quasi-diploid karyotypes similar to that of PSA4TG12, others are markedly aneuploid. Cell line EB26/1 and its clonal derivatives undergo adipogenesis in cultures maintained at confluence; in tumours formed by injection into syngeneic mice they produce muscle-like cells, cartilage and bone in addition to adipose cells. We therefore propose that EB26/1 and its clones are aneuploid derivatives of an uncommitted mesodermal cell. Cell line EB28/5 forms tumours with a histological appearance resembling that of yolk sac carcinoma but does not express biochemical markers characteristic of visceral or parietal endoderm. Cell line EB28/10n has a myoblast-like culture morphology and in tumours is capable of producing muscle-like cells, cartilage and bone. A high specific activity of alkaline phosphatase is present is two of five EB cell lines assayed, and plasminogen activator activity is present in all five. Since the EB cell lines represent populations of cells each expressing a particular subset of the genetic information present in a common ancestral genome, they will be invaluable for studying the developmental regulation of gene expression.
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PMID:Isolation of cell lines from differentiating embryonal carcinoma cultures. 668 50

The effects of two agents, 12-O-tetradecanoylphorbol-13-acetate (TPA) and deoxycholic acid (DOC), which act as tumor promoters in the gastrointestinal epithelium of experimental animals, were compared using primary cultures of human premalignant colonic epithelial cells at different stages in tumor progression. Both DOC and TPA enhanced the size of the proliferative fraction in colonies of early-stage premalignant cells, with DOC providing more stimulation. TPA-treated intermediate- and late-stage premalignant cells elongated and then disrupted the monolayer by forming rills several cells in thickness and then multicellular clusters. This multilayering was reminiscent of the areas of carcinoma found within adenomas. DOC had no such effects on morphology. Cell clustering was concomitant with secretion of a protease with characteristics of a plasminogen activator. Premalignant cells secreted severalfold higher levels of protease in response to TPA than did either TPA-treated primary cultures of colonic adenocarcinomas or established colon carcinoma cell lines. These results suggest that (a) DOC and TPA act sequentially during tumor promotion and (b) cell clustering and protease release may be associated with the transition of premalignant epithelial cells to colonic carcinoma.
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PMID:Differential response of premalignant epithelial cell classes to phorbol ester tumor promoters and to deoxycholic acid. 703 Apr 77

A human cell line has been established from a transplantable xenografted human testicular tumor, which, both in the original tumor and in the xenograft, exhibited the histological characteristics of an undifferentiated malignant teratoma (embryonal cell carcinoma). The cells in culture were undifferentiated by biochemical, morphological, and ultrastructural criteria, growing as small islands of cells that tended to form aggregates at high density. The cells showed some variation in chromosome number with 30 to 40% of the cells having a normal human karyotype. The cells expressed high levels of alkaline phosphatase, which by heat inactivation and inhibition studies was 40 to 50% placental type alkaline phosphatase. None of the cultures produced human chorionic gonadotrophin, alphafetoprotein, carcinoembryonic antigen, or fibronectin, although at high cell densities plasminogen activator could be detected at low levels. Cell surface studies showed that the cells shared antigens with the murine embryonal carcinoma cell line F9, expressed beta 2-microglobulin at very low and variable levels, and bound the lectin peanut agglutinin. These studies suggest that this cell line has some of the characteristics described for murine embryonal carcinoma cell lines.
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PMID:Characterization of a new human cell line derived from a xenografted embryonal carcinoma. 717 48

Harvest fluid concentrates (HFC's) from three human mammary tumor cell lines (T47D), HSO578T, and MDA-MB-157), one nontumorigenic human mammary cell line (HBL-100), and one mouse mammary tumor cell line (MCG-T14) stimulated thymidine incorporation in confluent quiescent BALB/c 3T3 cells in a dose-dependent manner. HFC's from all of the cell lines also exhibited plasminogen activator activity. Levels of mitogenic activity and plasminogen activator in the HFC preparations were not correlated with cell growth potential or with the amount of protein which was recovered in the HFC's. High levels of mitogenic activity and plasminogen activator in the HFC's from HBL-100 cells suggested that the production of these biological activities is not a unique feature of tumorigenic mammary cells. The HFC's from three human cell lines (T47D), HS0578T, MDA-MB-157) exhibited high levels of mitogenic activity but low levels of plasminogen activator. This suggested that plasminogen activator is not the source of the mitogenic activity in the HFC's from these cells. The HFC's from a human mammary carcinoma line, BT-20, contained very low levels of mitogenic activity and plasminogen activator. In addition, BT-20 HFC's inhibited the mitogenic activity of fetal bovine serum in a dose-dependent manner. It is proposed that BT-20 cells are the source of a macromolecular inhibitor of serum mitogens.
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PMID:Mitogenic activity and plasminogen activator in harvest fluid concentrates from mammary cells in culture. 719 75

A new epithelial cell line derived from undifferentiated carcinoma of human renal pelvis, designated KP 1, was established in vitro. The cell line has been passaged 190 times in vitro for 5 years and 9 months. The predominant cell in KP 1 was a tear-drop-shaped cell. Doubling time of the cell line was 35 h. The malignant epithelial character of this line was verified by carcinogenicity in the subcuticular layer of nude mice and by karyotypic analysis which revealed the cells to be completely aneuploid with a model chromosome number in the hypertriploid range. KP 1 cells were shown to produce both tissue thromboplastin and plasminogen activator which was immunologically identical to urokinase, the plasminogen activator in urine.
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PMID:Establishment of a human renal pelvic cancer cell line producing tissue thromboplastin and plasminogen activator. 720 Feb 72


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