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Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids.

Publication ,  Journal Article
Catherino, WH; Leppert, PC; Stenmark, MH; Payson, M; Potlog-Nahari, C; Nieman, LK; Segars, JH
Published in: Genes Chromosomes Cancer
July 2004

Uterine leiomyomas are prevalent estrogen-responsive clonal tumors, but the specific genetic alterations that contribute to their development have not been elucidated. To identify genes involved in the formation of leiomyomas, we used global expression profiling to compare clonal tumors with normal myometrium. Contrary to expectation, genes involved in estrogen action were not differentially expressed between leiomyoma and normal myometrium. Genes encoding extracellular-matrix proteins were prominently featured, suggesting their involvement in formation of a myofibroblast phenotype. Analysis of the extracellular matrix in the leiomyomas revealed a disordered collagen fibril orientation. Expression of the collagen-binding protein dermatopontin was found to be consistently decreased in leiomyoma by both reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR (mean underexpression = 9.41-fold) regardless of leiomyoma size, leiomyoma location, patient race, and patient age. This expression pattern was observed in 11 subjects and a total of 23 leiomyoma:myometrium pairs. Decreased expression of dermatopontin was also associated with keloid formation, a fibrotic disease that shares epidemiologic similarities with leiomyoma. Immunohistochemical studies of leiomyomas and keloids demonstrated reduced levels of dermatopontin in both tissues. In addition, ultrastructural analysis revealed that the orientation of the collagen fibrils in the keloid tissues strongly resembled that in the leiomyomas. Reduction in dermatopontin was associated with an increase in transforming growth factor-beta3 (TGFB3) mRNA levels in leiomyomas, whereas other genes involved in dermatopontin signaling were not differentially expressed. These findings suggest that leiomyoma development involves a myofibroblast cell phenotype characterized by dysregulation of genes encoding extracellular-matrix proteins. In particular, decreased expression of dermatopontin represents a molecular link between the leiomyoma and keloid phenotypes.

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Published In

Genes Chromosomes Cancer

DOI

ISSN

1045-2257

Publication Date

July 2004

Volume

40

Issue

3

Start / End Page

204 / 217

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Signal Transduction
  • RNA, Neoplasm
  • RNA
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Myometrium
  • Models, Genetic
  • Middle Aged
  • Microscopy, Electron
 

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Catherino, W. H., Leppert, P. C., Stenmark, M. H., Payson, M., Potlog-Nahari, C., Nieman, L. K., & Segars, J. H. (2004). Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Genes Chromosomes Cancer, 40(3), 204–217. https://doi.org/10.1002/gcc.20035
Catherino, William H., Phyllis C. Leppert, Matthew H. Stenmark, Mark Payson, Clariss Potlog-Nahari, Lynnette K. Nieman, and James H. Segars. “Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids.Genes Chromosomes Cancer 40, no. 3 (July 2004): 204–17. https://doi.org/10.1002/gcc.20035.
Catherino WH, Leppert PC, Stenmark MH, Payson M, Potlog-Nahari C, Nieman LK, et al. Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Genes Chromosomes Cancer. 2004 Jul;40(3):204–17.
Catherino, William H., et al. “Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids.Genes Chromosomes Cancer, vol. 40, no. 3, July 2004, pp. 204–17. Pubmed, doi:10.1002/gcc.20035.
Catherino WH, Leppert PC, Stenmark MH, Payson M, Potlog-Nahari C, Nieman LK, Segars JH. Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Genes Chromosomes Cancer. 2004 Jul;40(3):204–217.
Journal cover image

Published In

Genes Chromosomes Cancer

DOI

ISSN

1045-2257

Publication Date

July 2004

Volume

40

Issue

3

Start / End Page

204 / 217

Location

United States

Related Subject Headings

  • Uterine Neoplasms
  • Signal Transduction
  • RNA, Neoplasm
  • RNA
  • Oncology & Carcinogenesis
  • Oligonucleotide Array Sequence Analysis
  • Myometrium
  • Models, Genetic
  • Middle Aged
  • Microscopy, Electron