epidermal-growth-factor and Carcinoma--Signet-Ring-Cell

Topics: Adenocarcinoma, Papillary; Aged; Antineoplastic Agents; Carcinoma, Signet Ring Cell; DNA Mutational Analysis; Epidermal Growth Factor; Erlotinib Hydrochloride; Exons; Female; Humans; Immunohistochemistry; Mutation; Polymerase Chain Reaction; Quinazolines; Thyroid Neoplasms

A human signet ring gastric carcinoma cell line TSGH9201 was established in vitro. The cells grew in vitro as a monolayer with polygonal morphology and had a population doubling time of 34 hours. The cells secreted tumor markers CEA and CA 125. They were, however, not tumorigenic in athymic nude mice. Karyotypic analysis demonstrated a near tetraploidy with a modal chromosome number of 98. Northern blotting and immunocytochemical analysis revealed the expression of both transforming growth factor alpha and high levels of epidermal growth factor receptor. Cell growth was inhibited by the epidermal growth factor in vitro. The cell line may be a useful tool to study autocrine growth regulation through the epidermal growth factor receptor.

Topics: Animals; Blotting, Northern; Carcinoma, Signet Ring Cell; Cell Division; DNA, Neoplasm; Epidermal Growth Factor; ErbB Receptors; Gene Expression Regulation, Neoplastic; Humans; Mice; Mice, Nude; Polyploidy; RNA, Neoplasm; Stomach Neoplasms; Transforming Growth Factor alpha; Tumor Cells, Cultured

A cell line designated TSG6 was established from a signet-ring cell gastric carcinoma developed in a 57-year-old female patient. The TSG6 cells had well preserved the features of signet-ring cell carcinoma based on morphology. The cells exhibited both epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) immunoreactivities, and also secreted EGF. Moreover, the growth of TSG6 cells was stimulated in the presence of exogenous EGF. These results suggest that the possible presence of an EGF/EGFR autocrine growth mechanism is expressed in the TSG6 cells. The simultaneous treatment with EGF and 5-fluorouracil (5-FU) produced a nearly 2.4-fold enhancement of 5-FU cytotoxicity against TSG6 cells. A bromodeoxyuridine/DNA flow cytometry analysis revealed that EGF augmented 5-FU cytotoxicity by inducing the accumulation of S phase cells which might be more susceptible to 5-FU. Moreover, we found that the incorporation of 5-FU into the TSG6 cells was increased with the addition of EGF. These data indicate that EGF may be a potent agent as a biological response modifier for 5-FU against the tumors which express the EGF/EGFR autocrine mechanism, and that the TSG6 cell line is useful in furthering our understanding of the interaction between anticancer drugs and EGF.

Topics: Carcinoma, Signet Ring Cell; Cell Division; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Drug Synergism; Epidermal Growth Factor; Female; Flow Cytometry; Fluorouracil; Humans; Lymphatic Metastasis; Middle Aged; Stomach Neoplasms; Tumor Cells, Cultured

Expression of EGF, EGFR, TGF alpha, and PCNA in resected gastric carcinomas (15 cases of superspreading type and 25 cases of penetrating type) was immunohistochemically studied to understand biological features of these two types of gastric carcinomas. EGF, EGFR, and TGF alpha positive cases were preferentially found in the penetrating type rather than in the superspreading type (p < 0.05). Incidence of PCNA high expression cases in the penetrating type was significantly higher than that in superspreading type. Nineteen cases (76%) of the penetrating type and 1 case of the superspreading type (6.7%) were diffusely PCNA (+), and the incidence of in the former type was significantly higher than that of the latter type (p < 0.001). One case of the superspreading type and 13 cases of the penetrating type were either EGF (+) or TGF alpha (+), and EGFR (+), and the incidence in the latter type was significantly higher than that in the former type (p < 0.05), suggesting that growth and invasion of carcinoma cells, especially in the penetrating type, may depend on "autocrine mechanism". Incidence of the growth factors (+) and PCNA (+) cells in classical type of signet ring cells was lower than that in other types of singnet ring cells.

Topics: Carcinoma, Signet Ring Cell; Epidermal Growth Factor; ErbB Receptors; Humans; Immunohistochemistry; Neoplasm Invasiveness; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Stomach Neoplasms; Transforming Growth Factor alpha