PAX3 Is Extensively Expressed in Benign and Malignant Tissues of the Melanocytic Lineage in Humans

Abstract

We examined the potential interactions of anatomic site (head and arms versus trunk and legs) and CSD (CSD versus non-CSD melanoma) as proxy measures of sun exposure on the relationship between MC1R status (any variant) and BRAF-mutant melanoma. No statistically significant interactions were found (data not shown).In a study by Landi et al. (2006), D84E, R142H, and c.86_87insA were defined as ''r'' rather than ''R''. Reclassification of these variants as ''r'' did not significantly change the results (data not shown). For purposes of comparison with cases included by Landi et al. and Fargnoli et al., we repeated all analyses excluding two cases with melanomas on acral skin and four cases with positive or indeterminate germline CDKN2A mutations (Orlow et al., 2007). These reanalyses did not reveal any significant associations (data not shown).Our data do not support a strong association of MC1R variants with BRAF mutations in our North Carolina population. Differences in the findings between studies may be due, in part, to differing frequencies of distinct MC1R variants between study populations, which may not all be similarly associated with BRAF mutation. Another possibility is that the risk-modifying effect of MC1R variants may vary between populations based on unidentified genetic factors. Climate differences, such as ambient sun exposure, could also influence the relationship between MC1R status and BRAF-mutant melanoma. However, despite our study being the largest to date, the sample sizes are relatively modest in all the studies, and further investigation is necessary to clarify the relationship of germline MC1R variants and BRAF-mutant melanomas among different populations.

Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency

“…For Pax7/laminin double immunostaining, sections were fixed for 10 min in 2% PFA and antigen retrieval (required for optimal Pax7 detection) was performed by incubating slides in a solution consisting of 10 mM Tris (pH 9), 1 mM EDTA, 0.05% Tween 20 for 30 min at 97 °C and cooling slides in the same buffer at room temperature for 10 min (adapted from He et al, 2010). Slides were removed from retrieval buffer, allowed to air dry briefly, rinsed in Tris buffered saline (TBS) for 5 min and allowed to air dry briefly again.…”

PAX8 promotes tumor cell growth by transcriptionally regulating E2F1 and stabilizing RB protein

“…Approval for using archival specimens was obtained from the New Zealand Multi-Region Ethics Committee. Immunohistochemical staining was performed as described by He et al (2010). Sections were stained using a 3,3′-diaminobenzidine chromogen and couterstaining with hematoxylin.…”

PAX Genes in Cancer; Friends or Foes?

“…In this location Pax3 is involved in a transcriptional regulatory network to maintain the undifferentiated state of the melanocyte stem cells (Lang et al, 2005). Interestingly, PAX3 is also expressed in adult human epidermal melanocytes (He et al, 2010; Medic and Ziman, 2010), but in this location it appears PAX3 has retained only some of its developmental roles.…”

“…In addition, PAX3 is persistently expressed in embryonal rhabdomyosarcomas (Frascella et al, 1998). PAX3 expression has been reported in melanomas (Scholl et al, 2001; He et al, 2010), where it was initially thought that PAX3 expression is required for the regulation of MITF gene expression, as in the developing neural crest (reviewed in Kubic et al, 2008). MITF is a dominant regulator in the maintenance of plasticity during differentiation in both eye and melanoblast development (Jackson and Raymond, 1994).…”