Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma.
BACKGROUND
Aberrant activation of the hedgehog pathway has been identified in various human tumours, including familial and sporadic basal cell carcinomas (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to its receptor, patched protein (PTC), releases the inhibitory effect of PTC against smoothened protein (SMO), another protein of the SHH signalling pathway. The positive SMO signalling is not downregulated in BCCs because of the mutational inactivation of PTC. Recently, hedgehog-interacting protein (HIP) was found to bind to SHH directly and attenuate SHH signalling like PTC, while its expression was induced by SHH signals.


OBJECTIVE
To examine the expression patterns of HIP, SHH and PTC gene mRNA by human BCCs, in comparison with those by normal human skin and various skin tumours.


METHODS
We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin.


RESULTS
We found that the mRNA expression of both HIP and PTC genes was enhanced in all samples of BCCs, whereas none of the other skin tumours tested exhibited an increased level of such mRNAs as compared with normal skin. The transcription of the SHH gene, however, was at a baseline level in most BCCs.


CONCLUSIONS
These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs, and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene.
Tojo
M
M
Department of Dermatology, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima 960-1295, Japan. tojo@fmu.ac.jp
Kiyosawa
H
H
Iwatsuki
K
K
Kaneko
F
F
D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000072079:Patched Receptors; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; C117596:HHIP protein, human; D053823:Hedgehog Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000072079:Patched Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D015534:Trans-Activators