Molecular Characterization of Human MUC16 (CA125) in Breast Cancer

Abstract

The proposed study was aimed at understanding the role of MUC16 cytoplasmic tail (MUC16CT) in MUC16 mediated breast cancer pathogenesis and progression. To achieve this we proposed to understand the role of MUC16CT by carrying out over expression of MUC16CT in BC cells followed by performing various established in vitro and in vivo functional studies. To this end, we have generated FLAG-tagged MUC16CT-114FL and 114dCT stable transfectants in MDAMB231 and MCF7 breast cancer cells. Besides, our cell cycle analysis demonstrated that MUC16CT is responsible for the rapid G2/M transition (hence increased proliferation) compared to vector and 114dCT transfected MDAMB231 cells. Further functional studies are being undertaken. In another aim, we proposed to understand the mechanism of MUC16 mediated breast cancer progression. To this end, we demonstrated that MUC16CT is localized to the nucleus and is enriched on the chromatin bound fraction in a cytoplasmic tail dependent manner. Though the exact functional significance of the finding have not been elucidated, it is anticipated that MUC16CT might be bringing about a global transcriptional change by recruiting to the promoters of various genes probably by interacting with other transcription factors (as MUC16CT as such does not have any DNA-binding domain). In addition, we have demonstrated that MUC16CT is undergoing cleavage in the last SEA domain at a site other than the earlier predicted site. This will help us in accurately defining the role of MUC16CT in breast cancer pathogenesis. In addition, we have also demonstrated that MUC16CT undergoes post-translational modifications such as ubiquitination, which might alter its localization as well as signaling functions and stability. We are in the process of understanding the functional significance of such findings. Besides, mitochondrial localization of MUC16CT is evident.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2012
Accession Number
ADA560195

Entities

People

  • Srustidhar Das

Organizations

  • University of Nebraska Medical Center

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical Research
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Chromosome Structures
  • Diseases And Disorders
  • Epithelial Cells
  • Mass Spectrometry
  • Molecular Weight
  • Molecules
  • Neoplasms
  • Proteins
  • Spectrometry
  • Transcription Factors
  • Transitions

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Genetics
  • Oncology (Cancer Research).