Gene expression programs of human smooth muscle cells: tissue-specific differentiation and prognostic significance in breast cancers.
Smooth muscle is present in a wide variety of anatomical locations, such as blood vessels, various visceral organs, and hair follicles. Contraction of smooth muscle is central to functions as diverse as peristalsis, urination, respiration, and the maintenance of vascular tone. Despite the varied physiological roles of smooth muscle cells (SMCs), we possess only a limited knowledge of the heterogeneity underlying their functional and anatomic specializations. As a step toward understanding the intrinsic differences between SMCs from different anatomical locations, we used DNA microarrays to profile global gene expression patterns in 36 SMC samples from various tissues after propagation under defined conditions in cell culture. Significant variations were found between the cells isolated from blood vessels, bronchi, and visceral organs. Furthermore, pervasive differences were noted within the visceral organ subgroups that appear to reflect the distinct molecular pathways essential for organogenesis as well as those involved in organ-specific contractile and physiological properties. Finally, we sought to understand how this diversity may contribute to SMC-involving pathology. We found that a gene expression signature of the responses of vascular SMCs to serum exposure is associated with a significantly poorer prognosis in human cancers, potentially linking vascular injury response to tumor progression.
Chi
Jen-Tsan
JT
The Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, North Carolina, USA.
Rodriguez
Edwin H
EH
Wang
Zhen
Z
Nuyten
Dimitry S A
DS
Mukherjee
Sayan
S
van de Rijn
Matt
M
van de Vijver
Marc J
MJ
Hastie
Trevor
T
Brown
Patrick O
PO
D015415:Biomarkers; D001943:Breast Neoplasms / Q000175:diagnosis*; D001980:Bronchi / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D016000:Cluster Analysis; D018076:DNA, Complementary; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005801:Genes, Homeobox; D006801:Humans; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic
D015415:Biomarkers; D018076:DNA, Complementary