Relative expression of hMena11aand hMenaINVsplice isoforms is a useful biomarker in development and progression of human breast carcinoma

Noriyuki Tanaka, Hiroshi Yoshida, Yoshio Suzuki, Kenichi Harigaya

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Alternative splicing provides additional genomic complexity by producing multiple mRNAs and protein variants from any given gene. Splice variants have been identified in a large variety of cancer genes, suggesting that widespread aberrant and alternative splicing may be a consequence or even a cause of cancer. Human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoproteins (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. hMena has been shown to have several splice variants, including the hMenaINVisoform, expressed in invasive cancer cells, and the epithelialspecific isoform, hMena11a. We assessed the relative mRNA expression of hMena splice variants in 50 cases of invasive ductal breast carcinoma of no special type (IDC-NST) and 45 cases of ductal breast carcinoma in situ (DCIS) with special reference to non-neoplastic breast epithelial tissues. The samples were dissected from their respective regions by laser microdissection. Our results confirmed previous reports that hMenaINVexpression is augmented during tumor progression, while hMena11ais downregulated. Furthermore, simultaneous expression of hMena11aand hMenaINVwas found only in malignant lesions, while their expression was hardly detected in normal breast tissue and benign proliferative breast lesions. These results indicate that the higher relative expression of hMena11acompared with hMenaINVmay predict malignant transformation in breast epithelial cells, and, furthermore, a reversal of expression of hMena11aand hMenaINVmay dictate the state of cancer progression. Here, we demonstrate that determination of hMena11aand hMenaINVexpression could be a useful biomarker for predicting malignant behavior in breast epithelial lesions, and show that their relative expression is linked to adverse prognostic factors. Although the biological activity of the majority of alternatively spliced isoforms and their contribution to cancer biology has yet to be determined, their elucidation will have a large impact on therapeutic strategies for cancer.

Original languageEnglish
Pages (from-to)1921-1928
Number of pages8
JournalInternational Journal of Oncology
Volume45
Issue number5
DOIs
Publication statusPublished - Nov 1 2014
Externally publishedYes

Fingerprint

Human Development
Protein Isoforms
Biomarkers
Breast Neoplasms
Breast
Neoplasms
Alternative Splicing
Carcinoma, Ductal, Breast
Microdissection
Messenger RNA
Carcinoma, Intraductal, Noninfiltrating
Neoplasm Genes
Cell Movement
Actins
Proteins
Lasers
Down-Regulation
Epithelium
Epithelial Cells
Genes

Keywords

  • Breast
  • Ena/VASP
  • HMena
  • Invasive ductal carcinoma
  • Splicing isoform

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Relative expression of hMena11aand hMenaINVsplice isoforms is a useful biomarker in development and progression of human breast carcinoma. / Tanaka, Noriyuki; Yoshida, Hiroshi; Suzuki, Yoshio; Harigaya, Kenichi.

In: International Journal of Oncology, Vol. 45, No. 5, 01.11.2014, p. 1921-1928.

Research output: Contribution to journalArticle

Tanaka, Noriyuki ; Yoshida, Hiroshi ; Suzuki, Yoshio ; Harigaya, Kenichi. / Relative expression of hMena11aand hMenaINVsplice isoforms is a useful biomarker in development and progression of human breast carcinoma. In: International Journal of Oncology. 2014 ; Vol. 45, No. 5. pp. 1921-1928.
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AU - Tanaka, Noriyuki

AU - Yoshida, Hiroshi

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AU - Harigaya, Kenichi

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AB - Alternative splicing provides additional genomic complexity by producing multiple mRNAs and protein variants from any given gene. Splice variants have been identified in a large variety of cancer genes, suggesting that widespread aberrant and alternative splicing may be a consequence or even a cause of cancer. Human ortholog of mammalian enabled (hMena), a family of enabled/vasodilator-stimulated phosphoproteins (Ena/VASP), is an actin regulatory protein involved in the regulation of cell motility. hMena has been shown to have several splice variants, including the hMenaINVisoform, expressed in invasive cancer cells, and the epithelialspecific isoform, hMena11a. We assessed the relative mRNA expression of hMena splice variants in 50 cases of invasive ductal breast carcinoma of no special type (IDC-NST) and 45 cases of ductal breast carcinoma in situ (DCIS) with special reference to non-neoplastic breast epithelial tissues. The samples were dissected from their respective regions by laser microdissection. Our results confirmed previous reports that hMenaINVexpression is augmented during tumor progression, while hMena11ais downregulated. Furthermore, simultaneous expression of hMena11aand hMenaINVwas found only in malignant lesions, while their expression was hardly detected in normal breast tissue and benign proliferative breast lesions. These results indicate that the higher relative expression of hMena11acompared with hMenaINVmay predict malignant transformation in breast epithelial cells, and, furthermore, a reversal of expression of hMena11aand hMenaINVmay dictate the state of cancer progression. Here, we demonstrate that determination of hMena11aand hMenaINVexpression could be a useful biomarker for predicting malignant behavior in breast epithelial lesions, and show that their relative expression is linked to adverse prognostic factors. Although the biological activity of the majority of alternatively spliced isoforms and their contribution to cancer biology has yet to be determined, their elucidation will have a large impact on therapeutic strategies for cancer.

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KW - Splicing isoform

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