Biomedical subjects

Mikael Nilsson

Publications and source records attributed to Mikael Nilsson.

22 records · Page 2Linked to original sources

PubMed2002

Transforming growth factor-beta and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes.

Enhancement of tumor cell growth and invasiveness by transforming growth factor-beta (TGF-beta) requires constitutive activation of the ras/MAPK pathway. Here we have investigated how MEK activation by epidermal growth factor (EGF) influences the response of fully differentiated and growth-arrested pig thyroid epithelial cells in primary culture to TGF-beta1. The epithelial tightness was maintained after single stimulation with EGF or TGF-beta1 (both 10 ng/ml) for 48 hours. In contrast, co-stimulation abolished the transepithelial resistance and increased the paracellular flux of [(3)H]inulin within 24 hours. Reduced levels of the tight junction proteins claudin-1 and occludin accompanied the loss of barrier function. N-cadherin, expressed only in few cells of untreated or single-stimulated cultures, was at the same time increased 30-fold and co-localised with E-cadherin at adherens junctions in all cells. After 48 hours of co-stimulation, both E- and N-cadherin were downregulated and the cells attained a fibroblast-like morphology and formed multilayers. TGF-beta1 only partially inhibited EGF-induced Erk phosphorylation. The MEK inhibitor U0126 prevented residual Erk phosphorylation and abrogated the synergistic responses to TGF-beta1 and EGF. The observations indicate that concomitant growth factor-induced MEK activation is necessary for TGF-beta1 to convert normal thyroid epithelial cells to a mesenchymal phenotype.

Adherens Junctions↗

PubMed2002

Follicular growth of a thyroid carcinoma cell line (KAT-4) with abnormal E-cadherin and impaired epithelial barrier.

Loss of the epithelial phenotype is a well-established phenomenon during progression of carcinomas to a more malignant state. In the present study, we describe a human thyroid tumor cell line (KAT-4), established from a poorly differentiated carcinoma, which displays exceptional features. In culture, the KAT-4 cells had a fast proliferation rate that was not restricted by high cell density, resulting in multilayered growth. Unexpectedly, the cells expressed normal levels of epithelial markers, e.g., cytokeratin, occludin, and E-cadherin, showed apical-basolateral polarization of the plasma membrane including microvilli and junction complexes, and formed intercellular lumens resembling thyroid follicles. Yet, when grown on filter, the cells were unable to establish a tight paracellular barrier. Moreover, E-cadherin expressed at the cell surface consisted of two peptides with abnormal size (135 and 95 kd, respectively) as compared to mature E-cadherin (120 kd) in nonneoplastic thyrocytes. Northern blot analysis and examination of immunoreactivity, glycosylation, and catenin binding suggested that E-cadherin was aberrant because of altered posttranscriptional processing. Thus, the KAT-4 thyroid carcinoma cell line has a unique phenotype, with maintained epithelial morphology despite dysfunctioning tight junctions, abnormal E-cadherin, and loss of contact-inhibited growth, that is not previously identified in other wild-type tumor cell lines.

Aged↗

PubMed2002

Induction of discolored wood in Scots pine (Pinus sylvestris).

Induction of discolored wood in Scots pine (Pinus sylvestris L.) trees by treatment with ethylene, carbon dioxide, nitrogen (hypoxia) or wounding from early April to late September was investigated. All treatments induced formation of discolored wood upward and downward from the drill hole. The amount of discolored wood formed above the drill hole depended on the treatment in the following order: ethylene > carbon dioxide = nitrogen > wounding; and below the drill hole in the order: ethylene > carbon dioxide = nitrogen = wounding. Based on chemical analyses (HPLC/UV, GS/MS, LC/MS and 1H-NMR), discolored wood induced by wounding or treatment with ethylene or carbon dioxide showed compositional similarities to natural heartwood, whereas discolored wood induced by nitrogen treatment showed fewer similarities to natural heartwood. The results suggest that ethylene is an important factor controlling heartwood formation, although wounding and internal concentrations of carbon dioxide may also play a role.

Carbon Dioxide↗

PubMed2002

Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial cells.

UNLABELLED: The existence of thyroid stunning (i.e., inhibited thyroidal iodide uptake after administration of diagnostic amounts of (131)I) is controversial and is currently a subject of debate. To our knowledge, the stunning phenomenon has not been investigated previously in vitro. METHODS: Growth-arrested porcine thyroid cells that formed a tight and polarized monolayer in a bicameral chamber were irradiated with 3-80 Gy (131)I present in the surrounding culture medium for 48 h. The iodide transport capacity after irradiation was evaluated 3 d later by measuring the transepithelial (basal to apical) flux of trace amounts of (125)I. RESULTS: The basal-to-apical (125)I transport decreased with increasing absorbed dose acquired from (131)I; a nearly 50% reduction was observed already at 3 Gy. Stable iodide at the same molarity as (131)I (10(-8) mol/L) had no effect on the (125)I transport. Cell number and epithelial integrity were not affected by irradiation. CONCLUSION: Stunning of iodide transport is detected after (131)I irradiation of cultured thyroid cells. The degree of inhibition of transport is dependent on the absorbed dose.

Animals↗