CCHCR1 is up-regulated in skin cancer and associated with EGFR expression.
Despite chronic inflammation, psoriatic lesions hardly ever progress to skin cancer. Aberrant function of the CCHCR1 gene (Coiled-Coil alpha-Helical Rod protein 1, HCR) within the PSORS1 locus may contribute to the onset of psoriasis. As CCHCR1 is expressed in certain cancers and regulates keratinocyte (KC) proliferation in a transgenic mouse model, we studied its relation to proliferation in cutaneous squamous cell cancer (SCC) cell lines by expression arrays and quantitative RT-PCR and in skin tumors by immunohistochemistry. CCHCR1 protein was detected in the pushing border of SCC and lining basal cell carcinoma islands. Different from psoriasis, Ki67 had a similar expression pattern as CCHCR1. The most intense CCHCR1 staining occurred in areas positive for epidermal growth factor receptor (EGFR). Expression of CCHCR1 mRNA was upregulated 30-80% in SCC lines when compared to normal KCs and correlated positively with Ki67 expression. The most aggressive and invasive tumor cell lines (RT3, FaDu) expressed CCHCR1 mRNA less than non-tumorigenic HaCaT cells. Moreover, the tumor promoters okadaic acid and menadione downregulated CCHCR1 mRNA. We conclude that both in psoriasis and the early stages of KC transformation, CCHCR1 may function as a negative regulator of proliferation, but beyond a certain point in oncogenesis cannot control this phenomenon any longer.
Suomela
Sari
S
Department of Dermatology, Helsinki University Central Hospital and Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Elomaa
Outi
O
Skoog
Tiina
T
Ala-aho
Risto
R
Jeskanen
Leila
L
Pärssinen
Jenita
J
Latonen
Leena
L
Grénman
Reidar
R
Kere
Juha
J
Kähäri
Veli-Matti
VM
Saarialho-Kere
Ulpu
U
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D066246:ErbB Receptors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008214:Lymphocytes / Q000378:metabolism; D008954:Models, Biological; D011565:Psoriasis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000378:metabolism*; D015854:Up-Regulation
C412616:CCHCR1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D019394:Ki-67 Antigen; D066246:ErbB Receptors