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c-myb Proto-Oncogene Is Expressed by Quiescent Scleroderma Fibroblasts and, Unlike B-myb Gene, Does Not Correlate With Proliferation
- Source :
- Scopus-Elsevier
- Publisher :
- The Society for Investigative Dermatology, Inc. Published by Elsevier Inc.
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Abstract
- Systemic sclerosis (scleroderma) is characterized by excessive deposition of extracellular matrix constituents. Although it has been proposed that tissue fibrosis is due to increased fibroblast synthesis of various collagen polypeptides, there is some experimental evidence that patients with systemic sclerosis have a defect in the control of fibroblast growth. The myb family of genes includes, among others, the c-myb proto-oncogene and the structurally related gene, B-myb, which are both implicated in the regulation of differentiation and/or proliferation of hematopoietic and nonhematopoietic cells. To elucidate the molecular basis responsible for scleroderma fibroblast proliferation, we therefore elected to investigate the expression of c-myb and B-myb genes in scleroderma and control cells. Using the reverse transcriptase polymerase chain reaction technique, we detected c-myb transcripts in scleroderma skin fibroblasts rendered quiescent by serum deprivation. Under the same experimental conditions, c-myb message was not found in normal skin fibroblasts, but, after serum stimulation, c-myb RNA was clearly evident from 3 to 72 h in both normal and pathologic cells. Treatment of these cells with c-myb antisense oligonucleotides caused downregulation of c-myb expression, and the inhibition of scleroderma fibroblast proliferation was 42%, whereas in normal fibroblasts the inhibition was weaker (22%). In contrast to c-myb, in normal and scleroderma fibroblasts the level of expression of B-myb correlated with cell proliferation assessed by cell count, and densitometric analysis showed that B-myb message was 1.5-5 times higher in most of pathologic cells studied. The antisense B-myb oligonucleotides had a weaker antiproliferative effect compared with antisense c-myb, inhibiting scleroderma and normal fibroblasts by 23% and 13%, respectively. These data suggest that the B-myb and c-myb genes may play a role in scleroderma fibroblast proliferation and function.
- Subjects :
- Male
animal structures
Molecular Sequence Data
Cell
Gene Expression
Dermatology
Biology
Proto-Oncogene Mas
Biochemistry
Scleroderma
Extracellular matrix
Downregulation and upregulation
Gene expression
medicine
Animals
Humans
MYB
Fibroblast
Molecular Biology
Aged
Scleroderma, Systemic
Base Sequence
Oncogene
integumentary system
fungi
Oncogenes
Cell Biology
Fibroblasts
Middle Aged
Oligonucleotides, Antisense
Fetal Blood
medicine.disease
Molecular biology
medicine.anatomical_structure
Molecular Probes
Cancer research
Cattle
Female
Cell Division
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....c7e21e4d61273927eff656a761ebfaec
- Full Text :
- https://doi.org/10.1111/1523-1747.ep12348998