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Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy.

Publication ,  Journal Article
Horne, HN; Lee, PS; Murphy, SK; Alonso, MA; Olson, JA; Marks, JR
Published in: Mol Cancer Res
February 2009

Dysregulation of MAL (myelin and lymphocyte protein) has been implicated in several malignancies including esophageal, ovarian, and cervical cancers. The MAL protein functions in apical transport in polarized epithelial cells; therefore, its disruption may lead to loss of organized polarity characteristic of most solid malignancies. Bisulfite sequencing of the MAL promoter CpG island revealed hypermethylation in breast cancer cell lines and 69% of primary tumors analyzed compared with normal breast epithelial cells. Differential methylation between normal and cancer DNA was confined to the proximal promoter region. In a subset of breast cancer cell lines including T47D and MCF7 cells, promoter methylation correlated with transcriptional silencing that was reversible with the methylation inhibitor 5-aza-2'-deoxycytidine. In addition, expression of MAL reduced motility and resulted in a redistribution of lipid raft components in MCF10A cells. MAL protein expression measured by immunohistochemistry revealed no significant correlation with clinicopathologic features. However, in patients who did not receive adjuvant chemotherapy, reduced MAL expression was a significant predictive factor for disease-free survival. These data implicate MAL as a commonly altered gene in breast cancer with implications for response to chemotherapy.

Duke Scholars

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

February 2009

Volume

7

Issue

2

Start / End Page

199 / 209

Location

United States

Related Subject Headings

  • Wound Healing
  • Survival Rate
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proteolipids
  • Promoter Regions, Genetic
  • Prognosis
  • Oncology & Carcinogenesis
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Myelin Proteins
  • Molecular Sequence Data
 

Citation

APA
Chicago
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MLA
NLM
Horne, H. N., Lee, P. S., Murphy, S. K., Alonso, M. A., Olson, J. A., & Marks, J. R. (2009). Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. Mol Cancer Res, 7(2), 199–209. https://doi.org/10.1158/1541-7786.MCR-08-0314
Horne, Hisani N., Paula S. Lee, Susan K. Murphy, Miguel A. Alonso, John A. Olson, and Jeffrey R. Marks. “Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy.Mol Cancer Res 7, no. 2 (February 2009): 199–209. https://doi.org/10.1158/1541-7786.MCR-08-0314.
Horne HN, Lee PS, Murphy SK, Alonso MA, Olson JA, Marks JR. Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. Mol Cancer Res. 2009 Feb;7(2):199–209.
Horne, Hisani N., et al. “Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy.Mol Cancer Res, vol. 7, no. 2, Feb. 2009, pp. 199–209. Pubmed, doi:10.1158/1541-7786.MCR-08-0314.
Horne HN, Lee PS, Murphy SK, Alonso MA, Olson JA, Marks JR. Inactivation of the MAL gene in breast cancer is a common event that predicts benefit from adjuvant chemotherapy. Mol Cancer Res. 2009 Feb;7(2):199–209.

Published In

Mol Cancer Res

DOI

ISSN

1541-7786

Publication Date

February 2009

Volume

7

Issue

2

Start / End Page

199 / 209

Location

United States

Related Subject Headings

  • Wound Healing
  • Survival Rate
  • Reverse Transcriptase Polymerase Chain Reaction
  • Proteolipids
  • Promoter Regions, Genetic
  • Prognosis
  • Oncology & Carcinogenesis
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Myelin Proteins
  • Molecular Sequence Data