Gilbert, Jennifer L.
The Role of Bone Morphogenetic Protein (BMP) Signalling in Lung Cancer and Lung Regeneration.
PhD thesis, National University of Ireland Maynooth.
Bone morphogenetic proteins (BMPs) are members of the transforming growth
factor beta (TGFβ) super-family of signalling molecules. BMPs play crucial roles in
developing and adult tissues during processes including proliferation, differentiation,
apoptosis and epithelial-mesenchymal transition (EMT). However, little is known
regarding the role of BMPs in adult lungs during health and disease. In the present study,
the role of BMP signalling in lung cancer and lung regeneration processes was examined.
Early lung cancer tumours were isolated by laser capture microdissection from Kras
G12D mouse lungs and microarray analysis was carried out on RNA from the purified
populations of cells. Microarray and qPCR analyses revealed differential BMP pathway
expression during early tumour formation. BMPR expression was decreased compared to
normal lung epithelial cells while BMP4, BMP5, Smad4 and Id-1 expression were
We hypothesized BMPR-IB plays an anti-proliferative role during early tumour
progression. To characterise the function of BMPR-IB in lung cells, the gene was cloned
from mouse lung cDNA and an over-expression vector was generated. Viral and nonviral
delivery methods were assessed for their ability to efficiently transfect normal and
tumour-derived lung cells. Lipofectamine-2000 was the most efficient non-viral method
of gene delivery. This mode of transfection was utilised to transfect BMPR-IB gene into
the human BEAS-2B cell line, which is devoid of endogenous BMPR-IB expression. The
effects of BMPR-IB expression on proliferation, BMP signalling, and differentiation
were assessed. BMPR-IB expression caused a reduction in viable cell number, an
increase in non-viable cell number and an increase in cell death by apoptosis. Given the
loss of expression of BMPR-IB at the early stages of cancer, these data suggest that
BMPR-IB may have anti-proliferative properties during this stage in cancer.
The role of BMP signalling in lung regeneration processes was also examined in
the 1-NN acute lung damage. BMP signalling was up-regulated during the inflammatory
stage of lung damage. These data suggest that the BMP pathway plays an integral role
during regeneration and disease processes in the adult lung.
||Bone Morphogenetic Protein; BMP; Lung Cancer; Lung Regeneration;
||Faculty of Science and Engineering > Biology
||01 Feb 2011 16:30
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