PMID- 15946241 OWN - NLM STAT- MEDLINE DCOM- 20050914 LR - 20061115 IS - 0906-6705 (Print) IS - 0906-6705 (Linking) VI - 14 IP - 7 DP - 2005 Jul TI - Pigmentation in basal cell carcinoma involves enhanced endothelin-1 expression. PG - 528-34 AB - Basal cell carcinoma (BCC) is the most prevalent malignant skin tumor. In Asian patients, marked pigmentation in BCC lesions is often observed. Recently, endothelins (ETs) have been implicated to participate in the pigmentation process of BCC. Therefore, we set out to investigate the involvement of ET in the pigmentation process of BCC and the potential regulators in the pigmentation pathway. We explored the effects of an established BCC cell line on melanocytes. The growth factor profiles of BCC culture supernatant and effects of supernatant on melanocytes were documented. Potential regulators involved in the pigmentation pathway were also studied. The immunohistochemical staining of pigmented and non-pigmented BCC specimens was performed to confirm our in vitro findings. Our results showed that BCC supernatant contained significant amount of ET-1, basic fibroblast growth factor, and nerve growth factor. Furthermore, BCC supernatant stimulated melanin formation of cultured melanocytes. Addition of ET-receptor antagonist abrogated the melanogenic effect of BCC supernatant on melanocytes. Introduction of UVB irradiation decreased the ET-1 secretion by BCC cells. Immunohistochemical staining of the pigmented facial BCC specimens showed prominent expression of ET-1 on pigmented BCC, while the non-pigmented facial BCC specimens showed little ET-1 reactivity. Tumor necrosis factor-alpha (TNF-alpha) staining showed little expression on BCC specimens, regardless of pigmentation status. In summary, our results indicate that enhanced ET-1 expression in pigmented BCC plays an important role in the hyperpigmentation of this tumor. Moreover, this enhanced ET-1 cascade showed little correlation with UV irradiation and TNF-alpha expression in our study. FAU - Lan, Cheng-Che E AU - Lan CC AD - Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. FAU - Wu, Ching-Shuang AU - Wu CS FAU - Cheng, Chiu-Min AU - Cheng CM FAU - Yu, Chia-Li AU - Yu CL FAU - Chen, Gwo-Shing AU - Chen GS FAU - Yu, Hsin-Su AU - Yu HS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Denmark TA - Exp Dermatol JT - Experimental dermatology JID - 9301549 RN - 0 (Culture Media, Conditioned) RN - 0 (Endothelin-1) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 9061-61-4 (Nerve Growth Factor) SB - IM MH - Carcinoma, Basal Cell/*metabolism/pathology MH - Cell Movement MH - Cell Survival MH - Cells, Cultured MH - Culture Media, Conditioned MH - Endothelin-1/*metabolism MH - Fibroblast Growth Factor 2/metabolism MH - Humans MH - Immunohistochemistry MH - Keratinocytes/cytology/metabolism MH - Melanocytes/cytology/metabolism MH - Nerve Growth Factor/metabolism MH - Pigmentation/*physiology MH - Skin Neoplasms/*metabolism/pathology EDAT- 2005/06/11 09:00 MHDA- 2005/09/15 09:00 CRDT- 2005/06/11 09:00 PHST- 2005/06/11 09:00 [pubmed] PHST- 2005/09/15 09:00 [medline] PHST- 2005/06/11 09:00 [entrez] AID - EXD320 [pii] AID - 10.1111/j.0906-6705.2005.00320.x [doi] PST - ppublish SO - Exp Dermatol. 2005 Jul;14(7):528-34. doi: 10.1111/j.0906-6705.2005.00320.x.