In situ analysis of transforming growth factors-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) and TGF-beta type II receptor expression in basal cell carcinomas.
Transforming growth factor-beta (TGF-beta) consists of a highly homologous family of multifunctional peptides which are differentially expressed and function in a wide range of target cells. Aberrant expressions of TGF-beta s have been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions, and loss of TGF-beta growth inhibition may play a part in the progression of certain neoplasms. In the present study, we have analysed and compared, by in situ hybridization, mRNA expression of transforming growth factors-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) and TGF-beta type II receptor (T beta R II), and, by immunohistochemistry, the distribution of TGF-beta 3 protein in normal human skin and in basal cell carcinoma (BCC). The stroma of most BCCs revealed enhanced TGF-beta 1 and T beta R II mRNA expression when compared with normal dermis. A minority of BCCs also showed stromal overexpression of TGF-beta 2 and/or TGF-beta 3 mRNA. However, tumour tissues of all BCCs revealed weaker TGF-beta 3 mRNA and protein expression than normal interfollicular epidermis and hair follicle epithelia, whereas expression of TGF-beta 1 mRNA was comparably weak in tumour tissues and normal skin epithelia. Expression of TGF-beta 2 mRNA, which was clearly detectable in distinct hair follicle epithelia, was only barely detectable in normal interfollicular epidermis and in tumour tissues. In contrast, abundant T beta R II mRNA expression was observed both in normal skin epithelia and tumour tissues. From these findings, we suggest that increased stromal TGF-beta activity induces fibrotic alterations which promote tumour survival and/or progression via paracrine mechanisms, whereas lack of TGF-beta 3 expression by tumour cells may contribute to an autocrine growth control defect in BCCs.
Schmid
P
P
Department of Dermatology, University Basel, Switzerland.
Itin
P
P
Rufli
T
T
D002280:Basal Cell Carcinoma / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta