Expression of TGF-beta related Smad proteins in human epithelial skin tumors.

• Members of the transforming growth factor (TGF)-beta family regulate cell growth and differentiation activating intracellular Smad proteins. Their role in skin and skin tumorigenesis is not well understood. Therefore we investigated the expression of TGF-beta type I receptor (TbetaR-I) and Smad-proteins involved in the TGF-beta-pathway, e.g. Smad2, Smad3, Smad4, Smad6 and Smad7. We examined the effects of TGF-beta1, -beta2, BMP2, BMP7 on five epithelial cell lines in vitro. TGF-beta1-mediated growth inhibition of HaCaT and HSC4 were observed with half maximal effects at approximately 7 pg ml-1 and 20 pg ml-1, respectively. However, malignant HSC2 and A431 cells were unresponsive to TGF-beta1. A differentiation was seen after 5 days in HaCaT and HSC4 cells only. We compared the reactivity with specific antisera against TbetaR-I and Smad proteins among the different skin tumors: seborrheic keratoses (SK), actinic keratoses (AK), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). There were statistically significant differences of the ratio between the expression in tumor and that in non-tumorous epithelial cells in each tissue specimen. There was a tendency for the lower level of TbetaR-I expression of SCC compared with SK (p=0.08). This was accompanied by the decreased expression of the TbetaR-I. We found a markedly decreased expression of all antigens in BCC. conversion of normal keratinocytes to tumorigenic cells may in part be due to an acquisition of resistance to TGF-beta and loss of expression of intracellular signalling Smad proteins.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Activin Receptors

Type I

Amino Acid Sequence

Animals

Bone Morphogenetic Protein 2

Bone Morphogenetic Protein 7

Bone Morphogenetic Proteins

pharmacology

COS Cells

Carcinoma

Basal Cell

metabolism

pathology

Carcinoma

Squamous Cell

metabolism

pathology

Cell Differentiation

drug effects

Cell Line

DNA-Binding Proteins

biosynthesis

Humans

Keratinocytes

cytology

metabolism

Molecular Sequence Data

Neoplasm Proteins

biosynthesis

Protein-Serine-Threonine Kinases

biosynthesis

Receptors

Transforming Growth Factor beta

biosynthesis

Signal Transduction

Skin Neoplasms

metabolism

pathology

Smad2 Protein

Smad3 Protein

Smad4 Protein

Smad6 Protein

Smad7 Protein

Trans-Activators

biosynthesis

Transforming Growth Factor beta

metabolism

pharmacology

Tumor Cells

Cultured

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