RESUMEN
Tumor promoting phorbol esters, 12-O-tetradecanoylphorbol-13-acetate (TPA) and phorbol-12,13-dibutyrate (PDBu), significantly enhanced the growth of human gastric cancer cell line TMK-1, whilst activating protein kinase C. The time course of 125I-epidermal growth factor (EGF) binding to TMK-1 cells after TPA treatment showed a decrease in the number of EGF receptors on TMK-1 cells within 3 hr. Autophosphorylation of EGF receptor decreased in accordance with the decrease of EGF binding by TPA treatment. Scatchard plot analysis of TMK-1 cells after TPA treatment showed that high affinity EGF receptor disappeared at 3hr but the number of EGF receptors increased at 24 hr. These findings suggest that tumor promoting phorbol esters stimulate the cell growth through activation of protein kinase C and modification of EGF receptor of human gastric cancer cell line TMK-1.
Asunto(s)
Ésteres del Forbol/farmacología , Células Tumorales Cultivadas/efectos de los fármacos , División Celular/efectos de los fármacos , Línea Celular , Receptores ErbB/efectos de los fármacos , Receptores ErbB/metabolismo , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Células Tumorales Cultivadas/metabolismo , Células Tumorales Cultivadas/patologíaRESUMEN
A case of a synovial sarcoma arising in left axillary portion is reported. The structure of the tumor proved to be predominantly monophagic, through, immunohistochemically, the epithelial membrane antigen, keratin, and vimentin stained positively in the tumor cells in varying degrees. Electron microscopic observation revealed that some tumor cells were arranged in gland-like structures, with a desmosome-like attachment and fine microvilli in the luminal area.
Asunto(s)
Sarcoma Sinovial/patología , Neoplasias de los Tejidos Blandos/patología , Anciano , Axila , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Sarcoma Sinovial/ultraestructura , Neoplasias de los Tejidos Blandos/ultraestructuraRESUMEN
The effect of human epidermal growth factor (hEGF) on the growth of various histological types of six human gastric carcinoma cell lines was examined. The cell lines had relatively high affinity EGF receptors (dissociation constant Kd = 10(-9) to 10(-10) M). One gastric cancer cell line, MKN-74 (well differentiated adenocarcinoma) showed no response to hEGF, in cell growth, DNA synthesis or 125I-hEGF cell binding. There were no apparent correlations between histological type and cell growth, DNA synthesis or number of EGF receptors in these cells. The number of EGF receptors and the Kd value of the gastric carcinoma cell lines varied with their internal and external environments. hEGF concentrations corresponding to maximum stimulation in DNA synthesis varied between cell lines. The results suggest some gastric carcinoma cells to have EGF receptors and their growth seemingly to be stimulated by EGF in vitro. There are, however, no obvious correlations between the effect of hEGF on the growth of human gastric carcinoma cell lines or their histological type.
Asunto(s)
Adenocarcinoma/patología , Factor de Crecimiento Epidérmico/farmacología , Receptores ErbB/metabolismo , Neoplasias Gástricas/patología , Adenocarcinoma/metabolismo , División Celular/efectos de los fármacos , Línea Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Cinética , Neoplasias Gástricas/metabolismo , Temperatura , Factores de TiempoRESUMEN
Estrogen receptors (ER) in human gastric carcinomas were examined immunohistochemically using a specific monoclonal antibody to human ER. ER-immunoreactivity (ER-IR) was positive in 30 (27.8%) of the 108 gastric carcinomas examined. ER-IR was located in the nucleus of cancer cells. The incidence of ER-IR positive gastric carcinoma was not significantly different between male and female cases. However, the positive tumour cells were observed in 28 (39.4%) out of the 71 poorly differentiated adenocarcinoma, the incidence being significantly higher than that in well differentiated adenocarcinoma (p less than 0.01). There was no significant difference in the incidence of ER-IR between scirrhous carcinoma and non-scirrhous poorly differentiated adenocarcinoma. Synchronous expression of ER and epidermal growth factor receptor was found in 8 of the 26 scirrhous carcinomas (30.8%). Patients with ER-IR positive scirrhous gastric carcinomas showed a much worse prognosis than those with ER-IR negative scirrhous carcinomas.
Asunto(s)
Adenocarcinoma/análisis , Receptores de Estrógenos/análisis , Neoplasias Gástricas/análisis , Adenocarcinoma Mucinoso/análisis , Adenocarcinoma Papilar/análisis , Adenocarcinoma Escirroso/análisis , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
The effect of epidermal growth factor (EGF) on rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitro-soguanidine (MNNG) was studied. Male Wistar rats given MNNG for 30 weeks in drinking water (80 micrograms/ml) were treated with s.c. injections of human EGF (10 micrograms/kg, once daily) at various stages of the carcinogenesis. Four (30.8%) out of 13 rats treated with EGF immediately after cessation of the MNNG treatment had stomach tumors including one adenocarcinoma, one adenoma and two carcinoids. No stomach tumor was found in rats treated with MNNG alone or in those treated with MNNG and EGF for different periods such as synchronously for 10 weeks, for 30 weeks or throughout the experiment. These findings suggest a possible enhancing effect of EGF on stomach carcinogenesis in rats.
Asunto(s)
Factor de Crecimiento Epidérmico/farmacología , Metilnitronitrosoguanidina , Neoplasias Gástricas/inducido químicamente , Animales , Interacciones Farmacológicas , Masculino , Ratas , Ratas EndogámicasRESUMEN
A human cervical clear cell adenocarcinoma cell line was established and named SFCC. The tumor cells were obtained from ascites of a 39-year-old woman who underwent a radical hysterectomy. She had no history of exposure to diethylstilbestrol (DES). The histologic feature of the tumor cells at autopsy showed abundant clear cytoplasm with diastase digested glycogen granule growing in solid nest and tubular pattern. SFCC cells were continuously propagated in vitro during the past 29 months and grown in a monolayered sheet with a doubling time of about 67 hours. SFCC cells resembled the structure of the original tumor and had abundant glycogen granules, lipid droplets in the cytoplasm, and numerous microvilli. Immunohistochemically, SFCC cells had carcinoembryonic antigen (CEA) immunoreactivity in some parts of the cell population. Moreover, they had a relatively high amount of progesterone receptor (20.0 fmol/mg protein; kd, 6.6 nM) but did not have either an estrogen receptor or EGF receptor. The SFCC cell line secreted a high content of tissue peptide antigen (TPA) into the medium, indicating that the SFCC cell line is useful for analyzing the progesterone receptor and TPA production in clear cell adenocarcinoma of uterine cervix.
Asunto(s)
Adenocarcinoma/patología , Línea Celular , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/análisis , Adenocarcinoma/ultraestructura , Adulto , Amilasas , Animales , Biomarcadores de Tumor/análisis , Ciclo Celular , Línea Celular/análisis , Línea Celular/patología , Receptores ErbB/análisis , Femenino , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Neoplasias del Cuello Uterino/análisis , Neoplasias del Cuello Uterino/ultraestructuraRESUMEN
The effect of tyrosine kinase inhibitor, erbstatin, on cell growth and mRNA expression of growth-factor/receptor system was examined in 6 human gastric-carcinoma cell lines. Erbstatin inhibited both EGF-induced and serum-stimulated cell growth of all 6 cell lines (TMK-1, MKN-1, -7, -28, -45, -74) in a dose-dependent manner. 3H-thymidine incorporation by TMK-1 cells was also suppressed by erbstatin. Erbstatin inhibited protein kinase activity of EGF receptor, p185ERBB2 and pp60c-src in TMK-1 cells. The expression of mRNA of EGF receptor gene and ERBB-2 by TMK-1 cells was not changed by erbstatin treatment, whereas that of c-src was slightly decreased. Interestingly, erbstatin decreased membrane-bound TGF-alpha precursor as measured by anti-TGF-alpha antibody-binding assay, although mRNA expression for TGF-alpha was not altered by erbstatin. Our findings suggest that erbstatin may act as a growth inhibitor for human gastric-carcinoma cells and may not only inhibit tyrosine kinase activities but also negatively modulate the post-transcriptional step of TGF-alpha expression.
Asunto(s)
División Celular/efectos de los fármacos , Replicación del ADN/efectos de los fármacos , Receptores ErbB/genética , Hidroquinonas/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/genética , Proto-Oncogenes/efectos de los fármacos , ARN Mensajero/genética , Transcripción Genética/efectos de los fármacos , Factor de Crecimiento Transformador alfa/genética , Línea Celular , Medios de Cultivo , Factor de Crecimiento Epidérmico/farmacología , Receptores ErbB/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , Cinética , ARN Mensajero/efectos de los fármacos , Neoplasias GástricasRESUMEN
We examined pp60c-src protein kinase activity in human gastric carcinoma cell lines and gastric carcinoma tissues as well as normal mucosa. pp60c-src kinase activity was detected in all 5 carcinoma cell lines at various levels. Of 16 gastric carcinoma tissues, 8 showed higher pp60c-src kinase activity in tumor tissues than in corresponding normal mucosa. However, the levels of expression of pp60c-src detected by Western blotting were not always consistent with the activities of pp60c-src protein kinase. These findings suggest that the increase in pp60c-src protein kinase activity might be brought about by post-translational changes.