Neuronatin is related to keratinocyte differentiation by up-regulating involucrin.

Background: Neuronatin (Nnat), which is a neuronal developmental and differentiation molecule, is expressed in the endoplasmic reticulum of non-neuronal cells and is involved in insulin secretion from pancreatic β-cells by plausibly modulating their intracellular calcium concentration. However, the role of Nnat in keratinocyte differentiation remains unclear.

Objective: To unveil a possible integration of Nnat in controlling the keratinocyte differentiation markers such as involucrin, cytokeratin1, filaggrin, loricrin and S100A7.

Hematopoietic progenitor kinase 1, mitogen-activated protein/extracellular signal-related protein kinase kinase kinase 1, and phosphomitogen-activated protein kinase kinase 4 are overexpressed in extramammary Paget disease.

The c-Jun amino-terminal kinase (JNK) pathway seems to play important roles in the pathogenesis of several tumors, but its significance in extramammary Paget disease (EMPD) has not been investigated yet. The purpose of the study was to investigate the potential contribution of the JNK-associated molecules, such as hematopoietic progenitor kinase 1 (HPK1), mitogen-activated protein/extracellular signal-related protein kinase kinase kinase1 (MEKK1), transforming growth factor-β activated kinase 1 (TAK1), and phosphomitogen-activated protein kinase kinase 4 (p-MKK4) to the development of EMPD. Thirty-five paraffin-embedded EMPD specimens were subjected to immunohistochemical staining for HPK1, MEKK1, TAK1, and p-MKK4.

Nerve growth factor, brain-derived neurotrophic factor and their high-affinity receptors are overexpressed in extramammary Paget's disease.

Background: Neurotrophin (NT) systems appear to play important roles in the pathogenesis of several tumors, but their expression in extramammary Paget's disease (EPD) has not been investigated.

Methods: Thirty-four paraffin-embedded EPD specimens (32 primary EPD and 2 metastatic to lymph nodes) were subject to immunohistochemical staining for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), NT3, NT4, their high-affinity receptors (TrkA, TrkB and TrkC) and the common low-affinity receptor, p75 NT receptor (p75).

Results: All 34 EPD specimens, including 2 metastatic to lymph nodes, showed cytoplasmic overexpression of NGF, BDNF, TrkA and TrkB.

Aberrant expression of tenascin-c and neuronatin in malignant peripheral nerve sheath tumors.

Development of neurofibroma (NF) and its malignant counterpart, malignant peripheral nerve sheath tumor (MPNST), is a hallmark of type I neurofibromatosis (NF1). Newly identified glycoprotein neuronatin (Nnat) is predominantly expressed in the fetal central and peripheral nervous systems and is gradually diminished according to the neural maturation. However, its expression in NFs and MPNSTs is unknown.