Background: Both p75 and Par3 become localized in a polarized manner in Schwann cells. Results: BDNF activates Rac1 at the axon-glial interface, regulated by Par3, thereby facilitating proper alignment between the axon and Schwann cells. Conclusion: Polarized localization of Rac1 activation is critical for myelination. Significance: Par3 is involved in Rac1 activation by BDNF-p75 at the axon-glial interface, thereby promoting myelination.

Squamous cell carcinoma (SCC) and pre-malignant endobronchial lesions have been difficult to study in murine models. In this report, we evaluate the topical N-nitroso-tris-chloroethylurea (NTCU) murine SCC model, determine the extent to which resulting pre-malignant airway dysplasia develops, discuss clinicopathologic grading criteria in lesion progression, and confirm that immunohistochemical (IHC) staining patterns are consistent with those observed in human endobronchial dysplasia and SCC. Male and female FVB mice were treated biweekly with topical NTCU (4, 8, or 40mM) or vehicle for 32 weeks. Following sacrifice, squamous cell lesions were enumerated and categorized into the following groups: flat atypia, low-grade dysplasia, high-grade dysplasia, and invasive SCC. The 40mM NTCU concentration produced the entire spectrum of premalignant dysplasias and squamous cell carcinomas, but was associated with poor survival. Concentrations of 4mM and 8mM NTCU were better tolerated and produced only significant levels of flat atypia. Squamous origin of the range of observed lesions was confirmed with IHC staining for cytokeratin 5/6, p63, thyroid transcription factor-1 (TTF-1), and Napsin-A. This study demonstrates that topical application of high dose NTCU produces endobronchial pre-malignant lesions with classic squamous characteristics and should allow for improved pre-clinical evaluation of potential chemopreventive agents.

<p>PDF file - 1.3MB, H/E (A) and IHC staining of adenocarcinoma with CK5/6 (B), p63 (C), TTF-1 (D), and NAPSIN-A (E). magnification: 400X.</p>

<p>PDF file - 24K, Differences in lesion number between the males and females of the 40mM cohort.</p>

<p>PDF file - 99K, The number of animals in each score category from the behavioral index scoring system in the 4mM and 8mM treatment groups.</p>