HCR, a candidate gene for psoriasis, is expressed differently in psoriasis and other hyperproliferative skin disorders and is downregulated by interferon-gamma in keratinocytes.
We have previously shown that HCR is a good candidate gene for psoriasis based on its location in the PSORS1 locus, predicted secondary structure change of the associated allele, and expression pattern. To understand better the function of HCR, we studied how HCR expression is altered in hyperproliferative skin diseases other than psoriasis and in cancers. We examined also its regulation by different cytokines, growth factors, and antipsoriatic agents using quantitative RT-PCR (TaqMan) analysis and its location by immunostaining of keratinocyte cultures. Compared to psoriasis, HCR protein had a different distribution in chronic dermatitis, pityriasis rubra pilaris, mycosis fungoides, and chronic skin ulcers. In three of six grade III squamous cell carcinomas of the skin, four of four adenocarcinomas of the lung, and two of two ductal breast adenocarcinomas, positive cytoplasmic staining in cancer cells was detected. As in psoriasis, Ki67 did not colocalize with HCR. In cell cultures, HCR staining was detected perinuclearly in the cytoplasm and in the nuclei, suggesting that the protein may have a role in both compartments. A 2-fold downregulation of HCR mRNA expression was observed on stimulation with interferon-gamma. Based on the observations that HCR is detected in cancers of epithelial origin in Ki67-negative areas and that interferon-gamma downregulates its expression, we suggest it to have an antiproliferative function.
Suomela
Sari
S
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
Elomaa
Outi
O
Asumalahti
Kati
K
Kariniemi
Arja Leena
AL
Karvonen
Seija Liisa
SL
Peltonen
Juha
J
Kere
Juha
J
Saarialho-Kere
Ulpu
U
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001913:Bowen's Disease / Q000235:genetics / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D010144:Paget's Disease, Mammary / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D011565:Psoriasis / Q000235:genetics* / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C412616:CCHCR1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D007371:Interferon-gamma