Human patched (PTCH) mRNA is overexpressed consistently in tumor cells of both familial and sporadic basal cell carcinoma.
Recently, a human homologue of the Drosophila patched gene, PTCH, was identified as a putative tumor suppressor mutated in both hereditary and sporadic basal cell carcinomas. Because PTCH controls its own transcription, inactivating mutations in PTCH may lead to overexpression of mutant PTCH mRNA due to loss of autoregulation. The present study is aimed at evaluating whether deregulation of PTCH mRNA expression is a general feature of BCCs of varying histological growth pattern and malignant potential. Irrespective of histological subtype, PTCH mRNA was overexpressed consistently as determined by in situ hybridization in all of the sporadic (n = 16) and hereditary (n = 20) tumors examined. PTCH expression was found in all of the tumor cells but appeared stronger in the peripheral palisading cells. PTCH mRNA was not detected in adjacent nontumor epidermal cells or in other parts of the epidermis. In the majority of tumors (20 of 36), nuclear immunostaining for p53 was found in scattered cells, whereas seven tumors completely lacked p53 immunoreactivity. Our finding of an up-regulation of PTCH mRNA levels in all of the BCCs analyzed indicates that deregulation of the PTCH signaling pathway constitutes an early rate-limiting event in BCC development.
Undén
A B
AB
Department of Dermatology, Karolinska Hospital, Stockholm, Sweden.
Zaphiropoulos
P G
PG
Bruce
K
K
Toftgård
R
R
Ståhle-Bäckdahl
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019476:Insect Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D029721:Drosophila Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016159:Tumor Suppressor Protein p53; C070844:ptc protein, Drosophila