Differential response to retinoic acid of Syrian hamster embryo fibroblasts expressing v-src or v-Ha-ras oncogenes

1986 ◽  
Vol 6 (10) ◽  
pp. 3341-3348
Author(s):  
A M Jetten ◽  
J C Barrett ◽  
T M Gilmer
Keyword(s):  
Retinoic Acid ◽  
Tumor Cell ◽  
Cell Lines ◽  
Ornithine Decarboxylase ◽  
Syrian Hamster ◽  
Soft Agar ◽  
Protein Kinase Activity ◽  
Decarboxylase Activity ◽  
Oncogene Products ◽  
Transformed Cell Lines

It has been shown that treatment of many but not all tumor cell lines with retinoids affects cell proliferation and expression of the transformed phenotype. To determine whether the response of the tumor cell to retinoids is influenced by specific oncogenes activated in the cell, we studied the action of these agents in the immortal, nontumorigenic Syrian hamster embryo cell lines DES-4 and 10W transfected with either v-Ha-ras or v-src oncogenes. In this paper we show that in transformed DES-4 cells expressing v-src, retinoic acid inhibited anchorage-independent growth, reduced saturation density, and inhibited the induction of ornithine decarboxylase by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. In contrast, retinoic acid enhances the expression of the transformed phenotype in DES-4-derived cells that express v-Ha-ras. In these cells retinoic acid increases the number and the average size of colonies formed in soft agar. Moreover, retinoic acid enhances ornithine decarboxylase activity and acts in a synergistic fashion with 12-O-tetradecanoylphorbol-13-acetate. These results indicate that oncogenes activated in cells can indeed influence the response of cells to retinoids. Retinoic acid does not appear to alter the levels of pp60src or p21ras proteins in these cells, suggesting that retinoic acid does not affect the synthesis of these oncogene products. Furthermore, retinoic acid does not affect the protein kinase activity of pp60src. Transformed cell lines derived from 10W cells responded differently, indicating that the presence of a specific oncogene is not the only factor determining the response to retinoids. Possible mechanisms by which retinoic acid may interfere with the expression of the oncogene products are discussed.

scholarly journals Differential response to retinoic acid of Syrian hamster embryo fibroblasts expressing v-src or v-Ha-ras oncogenes.

1986 ◽  
Vol 6 (10) ◽  
pp. 3341-3348 ◽  
Author(s):  
A M Jetten ◽  
J C Barrett ◽  
T M Gilmer
Keyword(s):  
Retinoic Acid ◽  
Tumor Cell ◽  
Cell Lines ◽  
Ornithine Decarboxylase ◽  
Syrian Hamster ◽  
Soft Agar ◽  
Protein Kinase Activity ◽  
Decarboxylase Activity ◽  
Oncogene Products ◽  
Transformed Cell Lines

It has been shown that treatment of many but not all tumor cell lines with retinoids affects cell proliferation and expression of the transformed phenotype. To determine whether the response of the tumor cell to retinoids is influenced by specific oncogenes activated in the cell, we studied the action of these agents in the immortal, nontumorigenic Syrian hamster embryo cell lines DES-4 and 10W transfected with either v-Ha-ras or v-src oncogenes. In this paper we show that in transformed DES-4 cells expressing v-src, retinoic acid inhibited anchorage-independent growth, reduced saturation density, and inhibited the induction of ornithine decarboxylase by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. In contrast, retinoic acid enhances the expression of the transformed phenotype in DES-4-derived cells that express v-Ha-ras. In these cells retinoic acid increases the number and the average size of colonies formed in soft agar. Moreover, retinoic acid enhances ornithine decarboxylase activity and acts in a synergistic fashion with 12-O-tetradecanoylphorbol-13-acetate. These results indicate that oncogenes activated in cells can indeed influence the response of cells to retinoids. Retinoic acid does not appear to alter the levels of pp60src or p21ras proteins in these cells, suggesting that retinoic acid does not affect the synthesis of these oncogene products. Furthermore, retinoic acid does not affect the protein kinase activity of pp60src. Transformed cell lines derived from 10W cells responded differently, indicating that the presence of a specific oncogene is not the only factor determining the response to retinoids. Possible mechanisms by which retinoic acid may interfere with the expression of the oncogene products are discussed.

Cell surface topography in adhesion and detachment

1978 ◽  
Vol 36 (2) ◽  
pp. 300-301
Author(s):  
T.D. Allen
Keyword(s):  
Cell Lines ◽  
Thin Sheet ◽  
Liver Parenchyma ◽  
Soft Agar ◽  
Transformed Cells ◽  
Normal Cells ◽  
Epithelial Cell Lines ◽  
Normal Rat ◽  
Transformed Cell Lines ◽  
Peripheral Cytoplasm

The effects of trypsin and EGTA were investigated in parallel on two epithelial cell lines: a normal rat-liver parenchyma line (Fig. 1) and a spontaneously transformed line which had been subcloned in soft agar. The basic ultrastructural differences between these two cell lines has already been reported; briefly, the transformed cells, although typically epithelial in morphology, lack the well ordered microtubular and microfilamentous organisation of the normal cells but exhibit a marked increase in the number of surface microvilli.The reaction of each cell line to trypsination was broadly similar between the normal and transformed cell lines, with the transformed cells rounding up and detaching at a slightly quicker rate than the normals. In both cases the central region of the cell became domed with the peripheral cytoplasm being withdrawn in a thin sheet, some of which remained extended in short retraction fibrils (Fig. 2). Collection of the detached cells (after fixation in suspension) by aspiration onto silver filters showed the increased density of microvilli on the transformed cells to be maintained.

scholarly journals Effects of Febrile Temperature on Adenoviral Infection and Replication: Implications for Viral Therapy of Cancer

2005 ◽  
Vol 79 (1) ◽  
pp. 581-591 ◽  
Author(s):  
Stephen H. Thorne ◽  
Gabriel Brooks ◽  
Yeun-Ling Lee ◽  
Tina Au ◽  
Lawrence F. Eng ◽  
...  
Keyword(s):  
Viral Replication ◽  
Tumor Cell ◽  
Cell Lines ◽  
Therapeutic Index ◽  
Oncolytic Viruses ◽  
Transformed Cells ◽  
Hsp70 Expression ◽  
Tumor Cell Lines ◽  
Adenoviral Infection ◽  
Transformed Cell Lines

ABSTRACT We previously conducted a phase I/II study using arterial infusions of ONYX-015 (dl1520), a replication-selective adenoviral vector, with E1b deleted, for patients with metastatic colorectal cancer. No dose-limiting toxicities occurred, but >90% of the patients experienced fever. The effects of temperature on the replication of dl1520 in normal and transformed cells had not been studied. Therefore, replication and cell viability assays were performed with a panel of nontransformed and transformed cell lines cultured at 37 and 39.5°C and treated with adenovirus type 5 (Ad5) or dl1520. Ad5-mediated cytolytic effects were inhibited and production of infectious particles decreased by >1,000-fold in the nontransformed cells at 39.5°C. Seven of nine of the tumor cell lines retained significant cell-killing effects when treated with Ad5 at 39.5°C. When dl1520 was used, no cytolytic effects were observed at 39.5°C in the nontransformed cell lines; however, cytolytic effects occurred in six of nine tumor cell lines at 39.5°C. Notably, a subset of the tumor cell lines demonstrated increased dl1520-mediated cytolytic effect and replication at 39.5°C. Suppression of Ad5 and dl1520 replication at 39.5°C was not related to p53 status or HSP70 expression. Also, at 39.5°C, E1a expression was inhibited in nontransformed cells but was still abundant in the transformed cells, indicating that a novel early block in viral replication occurred in the nontransformed cells. Fever may therefore augment the therapeutic index of oncolytic viruses by inhibiting replication in normal cells while permitting or enhancing viral replication in some tumor cells.

scholarly journals Complement Factor D Is a Novel Biomarker and Putative Therapeutic Target in Cutaneous Squamous Cell Carcinoma

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 305
Author(s):  
Pegah Rahmati Nezhad ◽  
Pilvi Riihilä ◽  
Jaakko S. Knuutila ◽  
Kristina Viiklepp ◽  
Sirkku Peltonen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Cell ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Therapeutic Target ◽  
Normal Skin ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Epidermal Keratinocytes ◽  
Protein Kinase Activity

Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and normal human epidermal keratinocytes (NHEKs) demonstrated significant up-regulation of FD mRNA in cSCC cells compared to NHEKs. Western blot analysis also showed more abundant FD production by cSCC cell lines. Significantly higher FD mRNA levels were noted in cSCC tumors than in normal skin. Strong tumor cell-associated FD immunolabeling was detected in the invasive margin of human cSCC xenografts. More intense tumor cell-specific immunostaining for FD was seen in the tumor edge in primary and metastatic cSCCs, in metastases, and in recessive dystrophic epidermolysis bullosa-associated cSCCs, compared with cSCC in situ, actinic keratosis and normal skin. FD production by cSCC cells was dependent on p38 mitogen-activated protein kinase activity, and it was induced by interferon-γ and interleukin-1β. Blocking FD activity by Danicopan inhibited activation of extracellular signal-regulated kinase 1/2 and attenuated proliferation of cSCC cells. These results identify FD as a novel putative biomarker and therapeutic target for cSCC progression.

Sign in / Sign up

Export Citation Format

Share Document