LMO4 in lung development and cancer
Project type
Honours and/or PhD
| Supervisor(s) | Division | |
| (Primary) | Stem Cells and Cancer | .(JavaScript must be enabled to view this email address) |
| (Co-supervisor) | Stem Cells and Cancer | .(JavaScript must be enabled to view this email address) |
Details of project
LMO4 is a member of the LIM-only family of transcription regulators that act as molecular adaptors, providing a scaffold for multiprotein complexes of DNA-binding factors and transcriptional regulatory proteins. Immunohistochemistry using an anti-LMO4 antibody showed that LMO4 is highly expressed in epithelial tissues and more specifically in cells lining the airways of the developing and adult lung. Half of LMO4 knock-out mice were found to have exencephaly. LMO4-/- mice without exencephaly did not survive beyond the first day of birth. The lung pathology of LMO4-/- mice is yet to be described.
Deregulation of LMO4 has been described in several tumour types including breast, prostate, pancreas, lung and squamous cell carcinoma of the oral cavity. Microarray profiling of lung cancers showed that LMO4 was expressed abundantly in small cell lung cancer and advanced lung adenocarcinoma.
Using different lung-specific LMO4 conditional knock-out mice, this project aims to characterise the role of LMO4 during lung development and lung repair after injury. The role of LMO4 in lung cancer development will be evaluated using mouse models of lung cancer. LMO4 expression will be correlated with patient relapse-free survival and with markers of specific subtypes of lung cancers in tissue microarrays to establish the role of LMO4 as a putative new drug target for lung cancer therapy.
Project references
- Van Winkle LS, Buckpitt AR, Nishio SJ, Isaac JM & Plopper CG. Cellular response in naphthalene-induced Clara cell injury and bronchiolar epithelial repair in mice. Am J Physiol. 1995;269, L800-818.
- Visvader JE et al. The LIM domain gene LMO4 inhibits differentiation of mammary epithelial cells in vitro and is overexpressed in breast cancer. Proc Natl Acad Sci USA. 2001;98, 14452-14457.
- Hahm K, et al. Defective neural tube closure and anteroposterior patterning in mice lacking the LIM protein LMO4 or its interacting partner Deaf-1. Mol Cell Biol. 2004;24, 2074-2082.
- Taniwaki M, et al. Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer. Int J Oncol. 2006;29, 567-575.
Research interests
Our laboratory is interested in studying the cellular and molecular mechanisms underlying lung development and lung cancer formation.
A prerequisite to identifying the cells of origin in lung cancers is the isolation and characterisation of the normal stem cell and the hierarchy of cells that exist in the lung.
We aim to identify master regulators of stem cells and tumour-initiating cells within the lung to identify new targets for the development of future lung cancer therapies.
Selected publications
- Rawlins EL & Hogan BL. Epithelial stem cells of the lung: privileged few or opportunities for many? Development. 2006;133, 2455-2465.
- McQualter JL., Yuen K, Williams B & Bertoncello I. Evidence of an epithelial stem/progenitor cell hierarchy in the adult mouse lung. Proc Natl Acad Sci USA. 2010;107, 1414-1419.
Research theme
Cancer
Scientific discipline
- Cell Biology
- Developmental Biology
- Molecular Biology
- Stem Cell Biology
Keywords
lung development, cancer