Biomedical subjects

G Portella

Publications and source records attributed to G Portella.

42 records · Page 3Linked to original sources

PubMed1989

The Kirsten murine sarcoma virus induces rat thyroid carcinomas in vivo.

The injection of a retrovirus carrying the v-ras-Ki oncogene into the thyroid gland of adult Fischer rats induces thyroid carcinomas when associated with a treatment of the animals with a goitrogenic agent. More than one hundred adult Fischer rats have been treated with the goitrogen agent propylthiouracil in order to induce thyroid hyperplasia. Twenty days after treatment, rat thyroid glands, surgically prepared, were injected with the Kirsten murine sarcoma virus (KiMSV). Within three months more than 90% of the animals developed thyroid tumors. Histologically the tumors had the appearance of well differentiated carcinomas. Thirty animals had lung metastases in addition to the thyroid carcinoma. The presence of KiMSV specific transcripts and the specific transforming protein (p21) in thyroid carcinomas and in the metastases was detected by Northern blot analysis and immunoprecipitation, respectively. Only three rats, among thirty that had not received the goitrogen treatment, but only the injection with KiMSV, developed thyroid carcinomas of very small size and with a very long latency period (almost one year). The results described represent the first instance of thyroid carcinoma induction by retroviruses. This system may be regarded as a useful model to investigate the process of thyroid carcinogenesis in vivo. These results suggest that this model may also be useful for investigating the interaction between hormones and cells harboring the activated oncogene in the development of thyroid carcinoma since activated ras oncogenes have been implicated in human thyroid carcinoma.

Animals↗

PubMed1988

A retrovirus carrying the polyomavirus middle T gene induces acute thrombocythemic myeloproliferative disease in mice.

Mice inoculated with an artificially constructed retrovirus carrying the middle T gene of polyomavirus develop acute myeloproliferative disease with severe thrombotic and hemorrhagic disorder and impaired platelet function. The megakaryocytic lineage appears to be a target for polyoma-murine leukemia virus infection and middle T gene expression. This newly described disease represents a unique model system for studying disorders of the megakaryocytic lineage.

Adenosine Triphosphate↗

PubMed1988

Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression.

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

Animals↗

PubMed1987

One- and two-step transformations of rat thyroid epithelial cells by retroviral oncogenes.

A system of epithelial cells is described in which it is possible to study the number and the nature of genes capable of conferring the malignant phenotype. Two fully differentiated, hormone-responsive cell lines from rat thyroid glands are presented which are susceptible to one-step or two-step transformation upon infection with several murine acute retroviruses. After infection, both cell lines became independent from their thyrotropic hormone requirement for growth. However, complete transformation was achieved with one of the cell lines (FRTL-5 Cl 2), whereas the other cell line (PC Cl 3) failed to grow in agar and to give rise to tumors in vivo. The latter cell line was susceptible to complete transformation upon cooperation of the v-ras-Ha and the human c-myc oncogenes.

Animals↗

PubMed1985

A mos oncogene-containing retrovirus, myeloproliferative sarcoma virus, transforms rat thyroid epithelial cells and irreversibly blocks their differentiation pattern.

Differentiated, cloned rat thyroid epithelial cells (424 cells) were infected with a wild-type and a temperature-sensitive strain of the myeloproliferative variant of the Moloney murine sarcoma virus. The thyroid cells were productively infected and transformed by both virus strains and displayed some of the typical properties of malignant cells, such as morphological changes, growth in soft agar, and in vivo tumorigenicity. The acquisition of the transformed phenotype by the virus-infected cells was accompanied by a loss of the typical differentiated features of the thyroid epithelium, such as thyroglobulin (TG) secretion, iodide uptake, and dependence for growth on six factors including thyrotropin, the physiological thyroid stimulator. TG mRNA could not be demonstrated in cells transformed by both viral strains, suggesting a block at the level of the TG gene transcription. While the transformed state of the cell clones infected with the temperature-sensitive strain could be reverted by shifting the cultures to the temperature nonpermissive for transformation (39 degrees C), no reversion of the differentiated functions took place after such a shift, showing that the v-mos oncogene irreversibly shuts off the differentiation of thyroid epithelial cells in vitro. These results demonstrate, for the first time, an oncogenic potential of the v-mos oncogene family towards differentiated epithelial cells in vitro.

Animals↗

PubMedDate not supplied

Molecular mechanisms of invasion and metastasis during mouse skin tumour progression.

The ultimate stage of carcinogenesis in both human and mouse epithelial cells is the ability to invade surrounding tissues and metastasize to distant sites. In mouse skin tumours, the development of the invasive, spindle cell phenotype is associated with an imbalance of alleles on mouse chromosome 7, including the H-ras gene. In previous work, we have described clonally related squamous and spindle cell lines from the same primary tumour which differed substantially in morphology and behaviour, but showed the same series of mutations in H-ras and p53 genes. One of the events which takes place during this transition is disruption of cell-cell contacts, possibly due to the induced expression of metalloproteinases such as stromelysin-1 and disappearance of the cell adhesion molecule E-cadherin. Parallel studies using somatic cell hybrids have shown that the spindle cell phenotype is recessive in hybrids between squamous and spindle cells. We propose that an important epidermal differentiation-controlling gene is lost during the spindle cell transition.

Animals↗