Increased expression of TGF-beta/Smad proteins in basal cell carcinoma.
BACKGROUND
Basal cell carcinoma (BCC) is the most common cancer in humans placing a significant burden on healthcare services worldwide. There is an increasing evidence that the development of cutaneous epithelial tumours is pathogenetically linked to dysregulations of the transforming growth factor beta (TGF-beta) and its signalling molecules, the Smads.


OBJECTIVE
In the present study we aimed to investigate the mRNA as well as protein expression of TGF-beta/ Smad signalling proteins in patients with BCC and healthy controls.


METHODS
In this prospective pilot study, 24 patients with BCC were recruited. Punch biopsies were harvested from the centre of the tumour (lesional) as well as an adjacent healthy skin site (non-lesional controls). In addition to the specimens of BCC patients, skin samples (healthy controls) were obtained from subjects who had no history of skin cancer (n = 25). Real-time RT-PCR as well as immunohistochemistry was performed. -


RESULTS
The mRNA levels of TGF-b/Smad transducers observed in healthy controls did not significantly differ from TGF-beta/Smad levels observed in non-lesional skin of BCCs patients (P > 0.05). RT-PCR revealed significant mRNA overexpression of TGF-beta1, Smad3, and Smad7 in BCCs as compared to non-lesional skin (P < 0.05). TGF-beta1 mRNA expression significantly correlated with Smad3 (r = 0.60; P < 0.05) and Smad7 (r = 0.76; P < 0.05) levels. Immunohistochemistry demonstrated marked protein overexpression of Smad3 in tumour tissue as compared to non-lesional skin.


CONCLUSIONS
Our data suggest a possible role of TGF-beta/Smad signalling in the pathogenesis of BCC.
Gambichler
T
T
Department of Dermatology, Ruhr-University Bochum, Gudrunstr. 56, 44791 Bochum, Germany. t.gambichler@klinikum-bochum.de
Skrygan
M
M
Kaczmarczyk
J M
JM
Hyun
J
J
Tomi
N S
NS
Sommer
A
A
Bechara
F G
FG
Boms
S
S
Brockmeyer
N H
NH
Altmeyer
P
P
Kreuter
A
A
D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D051785:Smad Proteins; D016212:Transforming Growth Factor beta