Functional analysis of alternative isoforms of the transcription factor PAX3 in melanocytes in vitro.
Transcription factor PAX3 has seven isoforms of which PAX3c has been studied extensively whereas the functions of the other isoforms are less well known. Here, we found that PAX3 isoforms in a stable transfection system have different biological functions in mouse melanocytes in vitro. PAX3a and PAX3b had negative effects on melanocyte proliferation but had no discernable effect on melanocyte growth in soft agar. PAX3a did not affect cell migration and apoptosis but PAX3b reduced migration and accelerated apoptosis. PAX3c and PAX3d promoted cell proliferation, migration, transformation, and survival. PAX3e reduced melanocyte growth; transformation and migration were unchanged and apoptosis was increased in vitro. PAX3g did not influence cell proliferation or apoptosis. Cells expressing PAX3g were able to grow in soft agar but migration was reduced. PAX3h increased cell proliferation, migration, survival, and transformation. These functional studies have advanced our understanding of the effects of PAX3 isoforms in melanocytes and their potential contribution in tumorigenesis.
Wang
Qiuyu
Q
School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester, United Kingdom.
Kumar
Shant
S
Slevin
Mark
M
Kumar
Patricia
P
D002453:Cell Cycle; D002455:Cell Division; D045744:Cell Line, Tumor; D002465:Cell Movement; D047108:Embryonic Development / Q000502:physiology; D006801:Humans; D008544:Melanocytes / Q000166:cytology / Q000502:physiology*; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D009432:Neural Crest / Q000502:physiology; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000502:physiology; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D020033:Protein Isoforms; D012334:RNA, Neoplasm