Sample A: Cover Page of Thesis, Project, or Dissertation Proposal

lacking p53 mutations [30]. While, we observed significant up-regulation of stratifin in the
Bhattacharjee squamous samples, the adenocarcinoma samples demonstrated minimal presence of
p53 mRNA. It is our belief that these gene levels suggest that a flawed cytokinesis process is
occurring in these samples. Further support of this are the presence of ARPC2 and TNIK, both of
which regulate the actin cytoskeleton [32-34].
These results may also indicate that the squamous samples are more proficient at attaining
appropriate G2 sequesence, although in the prolonged G2 state they may be incurring an
accumulation of ROS, causing DNA-damage. Additional support for the occurrence of DNA-
damage is the association of condensing-1 with PARP (poly ADP-ribose polymerase), supporting
the role of condensing-1 in DNA repair [35]. Similarly, TTF-1 has been shown to interact with
PARP2 to regulate the expression of surfactant protein B [36].
Surfactant protein B (SPB) and keratin 6A both were significantly up-regulated in the squamous
samples and slightly up-regulated in the adenocarcinoma samples. Surfactant protein B is a 79
amino acid hydrophobic peptide which is expressed in alveolar type epithelial cells and clara cells
of the lung [37-41]. This peptide is essential in maintaining normal lung functions and surface
membrane structure, by reducing the surface tension [37]. The up-regulation of this peptide may
be a compensation for the toxic exposure of lung tissue to cigarette smoke: the link to TTF1 is
tantalizing. TTF1’s DNA binding activity of SPB is well documented [36, 38, 39]. Interference
of TTF1 binding has been reported to be caused by ceramide [39], PARP-2 [36], and proteosome
dysfunction [38]. Coupled histological staining for TTF1, KRT6A, and p63 has recently been
evaluated for NSCLC classification [42]; additionally, p63 and KRT6A have been associated
with more aggressive tumors [43].
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