title: Identification of Differentially Expressed K-Ras Transcript Variants in Patients With Leiomyoma.
abstract: Molecular studies have demonstrated a wide range of gene expression variations in uterine leiomyoma. The rat sarcoma virus/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase (RAS/RAF/MAPK) is the crucial cellular pathway in transmitting external signals into nucleus. Deregulation of this pathway contributes to excessive cell proliferation and tumorigenesis. The present study aims to investigate the expression profile of the K-Ras transcripts in tissue samples from patients with leiomyoma.
  
  
  
  The patients were leiomyoma cases who had no mutation in mediator complex subunit 12 ( MED12) gene. A quantitative approach has been applied to determine the difference in the expression of the 2 main K-Ras messenger RNA (mRNA) variants. The comparison between gene expression levels in leiomyoma and normal myometrium group was performed using relative expression software tool.
  
  
  
  The expression of K-Ras4B gene was upregulated in leiomyoma group ( P = .016), suggesting the involvement of K-Ras4B in the disease pathogenesis. Pairwise comparison of the K-Ras4B expression between each leiomyoma tissue and its matched adjacent normal myometrium revealed gene upregulation in 68% of the cases. The expression of K-Ras4A mRNA was relatively upregulated in leiomyoma group ( P = .030). In addition, the mean expression of K-Ras4A gene in leiomyoma tissues relative to normal samples was 4.475 (95% confidence interval: 0.10-20.42; standard error: 0.53-12.67). In total, 58% of the cases showed more than 2-fold increase in K-Ras4A gene expression.
  
  
  
  Our results demonstrated increased expression of both K-Ras mRNA splicing variants in leiomyoma tissue. However, the ultimate result of KRAS expression on leiomyoma development depends on the overall KRAS isoform balance and, consequently, on activated signaling pathways.
authors.affiliation: 1 Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Zolfaghari
authors.affiliation: 2 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Shahbazi
authors.affiliation: 3 Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Mahnaz
authors.initials: M
authors.lastname: Torfeh
authors.affiliation: 3 Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Khorasani
authors.affiliation: 1 Department of Molecular Genetics, Tehran Medical Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Hashemi
authors.affiliation: 3 Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Mahdian
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007889:Leiomyoma / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation; D009215:Myometrium / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C117307:KRAS protein, human; D020033:Protein Isoforms; D016283:Proto-Oncogene Proteins p21(ras)
keywords: K-RAS gene; leiomyoma; real-time PCR; transcript variants