Dysregulated expression of transforming growth factor beta and its type-I and type-II receptors in basal-cell carcinoma.
In mammals, transforming growth factor-beta (TGF-beta) is found in 3 highly homologous isoforms that exert their effects via heteromeric complexes of type-I and type-II receptors (TbetaR-I and TbetaR-II). TGF-beta regulates the growth and metabolism of various cell types, including keratinocytes. We have investigated the immunohistological localization of TGF-beta1, TGF-beta2, TbetaR-I and TbetaR-II in normal human skin, basal-cell carcinoma (BCC), Bowen's disease, seborrheic keratosis, eccrine poroma and eccrine spiradenoma using frozen tissue specimens. In normal human skin, the immunoreactive TGF-beta2, but not TGF-beta1, was detected predominantly in the epidermis, follicles and sebaceous glands. The epidermal expression of TbetaR-I and TbetaR-II was very weak in the majority of normal skins. In BCC, TGF-beta2 expression was markedly reduced or completely negative. In addition, TbetaR-I- and TbetaR-II-positive stromal cells were accumulated in the fibrotic stroma in some BCCs. These stromal cells were partly but moderately positive for TGF-beta1. Decreased expression of TGF-beta2 was likely to be associated with the differentiation state of BCC cells, since TGF-beta2 expression was clearly observed in the squamoid foci of BCC. In addition, no expression of TGF-beta2 was detected in the eccrine secretory portion or in eccrine spiradenoma, but it was detected in the upper eccrine ducts and in eccrine poroma.
Furue
M
M
Department of Dermatology, University of Tokyo, Branch Hospital, Bunkyo-ku, Japan. FURUEM-DIS@h.u-tokyo.ac.jp
Kato
M
M
Nakamura
K
K
Nashiro
K
K
Kikuchi
K
K
Okochi
H
H
Miyazono
K
K
Tamaki
K
K
D018250:Acrospiroma / Q000235:genetics / Q000378:metabolism; D030201:Activin Receptors, Type I; D006607:Adenoma, Sweat Gland / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001913:Bowen's Disease / Q000235:genetics / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017492:Keratosis, Seborrheic / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013544:Sweat Gland Neoplasms / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics
D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II