ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00049.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The present study was carried out to investigate the abundance of tyrosinase and related proteins (TRP‐1 and TRP‐2) in human epidermis and their relationship to melanin type. Positive immunocytochemical staining was seen for all three proteins in epidermal melanocytes. For each protein the numbers of positively stained melanocytes were similar in all subjects studied irrespective of skin type. Following 5 daily suberythemal doses of UVB the melanocytes were larger, more dendritic, and increased in number. With TRP‐1 and TRP‐2 the increase in number in response to UVB was unrelated to skin type and, hence, with melanin type but with tyrosinase there was a much greater increase in skin types III and IV than in skin type I and II. The enhanced numbers of tyrosinase‐positive melanocytes were accompanied by increased staining intensity, suggesting a greater expression of tyrosinase in the melanocytes from skin types III and IV compared with skin types I and II. This increase in tyrosinase could be related to the greater levels of eumelanin found in skin types III and IV, and this is in keeping with the view that higher levels of tyrosinase are associated with the production of eumelanin than pha

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00050.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

In the Silky Fowl (SF) breed of chicken, most of the internal organs are infiltrated with melanocytes. Previous studies have shown that this generalized mesodermal pigmentation is not due to a cell autonomous abnormality of the melanocytes but to environmental factors able to promote both the homing of pigment cell precursors in abnormal embryonic sites and their proliferation and differentiation.To analyse the mode of these environmental cues, we tested the effect of SF embryo extract (SFEE) on cultured quail neural crest cells as compared with that of EE from normal chickens of the JA57 strain (JA57EE). We found that SFEE enhances crest cell proliferation as judged by3H‐TdR incorporation and cell counting. In contrast, no effect of SFEE was observed either on the proportion of cultured cells that are engaged into the melanocytic differentiation pathway or on the amount of melanin produced by each differentiated pigment cell. The simple observation, however, reveals that SFEE has a significant effect on pigmentation of the cultured quail neural crest cells. This effect has therefore to be accounted for by the general increase in cell number induced by SFEE. The question is raised as to whether the in vivo SF phenotype is generated exclusively by this mechanis

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00051.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Although the administration of melanocyte‐stimulating hormone (MSH) peptides results in skin darkening in man, cultured human melanocytes have been reported to be unresponsive to these peptides. This may be a consequence of the conditions under which the cells were maintained in vitro, particularly the use of phorbol esters and cholera toxin as melanocyte mitogens. By culturing the cells in the absence of these additives, we demonstrate that α‐MSH and its synthetic analogue Nle4DPhe7α‐MSH (NDP‐MSH) induce dose‐related increases in melanin content and tyrosinase activity and affect cell morphology in the majority of human melanocyte cultures. In addition, NDP‐MSH induces increases in tyrosinase mRNA and tyrosinase‐related protein‐1 (TRP‐1) mRNA. The dose‐response curves for the MSH peptides are sigmoidal and the two peptides are equipotent in their effects on human melanocytes. Adrenocorticotropic hormone (ACTH) also affects morphology and stimulates melanogenesis and tyrosinase activity in human melanocytes. However, the dose‐response curves for ACTH are biphasic, and the melanocytes respond to lower concentrations of ACTH than MSH peptides, similar to those normally present in human plasma. These findings may be important in understanding the role of these pro‐opiomelanocortin peptides i

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00052.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Tamoxifen plays a major role in the management of breast cancer in women and is currently used to a lesser extent in other neoplasias. Many of the pharmacological properties of tamoxifen are consistent with anti‐estrogen activity, but it also has significant, although lesser, benefit in patients whose tumours are estrogen‐receptor negative. We recently reported that murine B16 melanoma cell attachment to extracellular matrix proteins can be inhibited by calmodulin antagonists. In seeking a calmodulin antagonist that could be used clinically, we investigated tamoxifen, which is known to have calmodulin antagonist activity in vitro, and confirmed that it will inhibit murine melanoma cell attachment in vitro. In the current study, we examined the effect of tamoxifen on the attachment of human ocular melanoma cell lines to a range of extracellular matrix substrates to evaluate the potential relevance of calmodulin antagonists, including tamoxifen, to reducing metastatic spread of these tumours. We report that six ocular melanoma cell lines established from choroidal melanoma tumours showed rapid attachment to a range of substrates and that this attachment can be significantly reduced by an experimental calmodulin antagonist (J8) and by tamoxifen. In summary, we conclude that the ability of calmodulin antagonists, including tamoxifen, to inhibit ocular melanoma cell attachment to matrix proteins in vitro merits further investigation as it may offer another approach to reducing metastatic spread of these tumo

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00053.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Tyrosinase‐related protein 1 (TRP1) maps to thebrownlocus in mice. Although the specific function of TRP1 has been in dispute, mutations in its structural gene result in the formation of brown rather than black melanin. We have investigated the melanogenic function of TRP1 by using immune‐affinity purification of the protein and also by using transfection of its gene into fibroblasts to study its characteristics. We show that TRP1 has the ability to oxidize DHICA, a melanogenic intermediate derived from DOPAchrome. In addition, TRP1 has the ability to interact with tyrosinase and significantly stabilize the latter's catalytic funct

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00054.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Human melanoma cell lines have been used to examine the regulation of the tyrosinase (TYR) and tyrosinase‐related protein genes TRP‐1 and TRP‐2 in response to differentiating chemicals and UV irradiation. TRP‐1 mRNA levels can be repressed by treatment with the differentiating chemicals DMSO and HMBA. There is little effect of UV irradiation on pigment synthesis by human melanoma cell lines or tyrosinase activity, with variable effects on the levels of the TYR, TRP‐1, and TRP‐2 gene transcripts. The human TRP‐1 gene promoter has been isolated and its activity tested by transient cell transfection to begin an examination of signal transduction mechanisms operating in response to pigmenting and differentiating agents. To identify transcription factors that may be involved in melanocytic gene expression, we studied the N‐Oct‐3 and N‐Oct‐5 octamer‐binding activities normally expressed in the neuroectodermal cell lineage and which are expressed at high levels in melanoma cells. POU‐domain‐containing cDNA have been isolated from the A2058 human melanoma cell line that are homologous to thebrn‐2 gene tha

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00055.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00056.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00057.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00058.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY