Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9

Dengfeng Cao, Kornelia Polyak, Marc K. Halushka, Hind Nassar, Nina Kouprina, Christine Iacobuzio-Donahue, Xinyan Wu, Saraswati Sukumar, Jessica Hicks, Angelo De Marzo, Pedram Argani

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Introduction: Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed.Methods: We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR).Results: We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RT-PCR analysis of the index case.Conclusions: We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS.

Original languageEnglish (US)
Article numberR91
JournalBreast Cancer Research
Volume10
Issue number5
DOIs
StatePublished - Oct 27 2008
Externally publishedYes

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Claudin-4
Matrix Metalloproteinase 9
Down-Regulation
Gene Expression
Transcriptome
Reverse Transcriptase Polymerase Chain Reaction
Breast
Breast Carcinoma In Situ
Epithelium
Immunohistochemistry
Lobular Carcinoma
Intercellular Junctions
Gene Expression Profiling
Gene Library

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. / Cao, Dengfeng; Polyak, Kornelia; Halushka, Marc K.; Nassar, Hind; Kouprina, Nina; Iacobuzio-Donahue, Christine; Wu, Xinyan; Sukumar, Saraswati; Hicks, Jessica; De Marzo, Angelo; Argani, Pedram.

In: Breast Cancer Research, Vol. 10, No. 5, R91, 27.10.2008.

Research output: Contribution to journalArticle

Cao, D, Polyak, K, Halushka, MK, Nassar, H, Kouprina, N, Iacobuzio-Donahue, C, Wu, X, Sukumar, S, Hicks, J, De Marzo, A & Argani, P 2008, 'Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9', Breast Cancer Research, vol. 10, no. 5, R91. https://doi.org/10.1186/bcr2189
Cao, Dengfeng ; Polyak, Kornelia ; Halushka, Marc K. ; Nassar, Hind ; Kouprina, Nina ; Iacobuzio-Donahue, Christine ; Wu, Xinyan ; Sukumar, Saraswati ; Hicks, Jessica ; De Marzo, Angelo ; Argani, Pedram. / Serial analysis of gene expression of lobular carcinoma in situ identifies down regulation of claudin 4 and overexpression of matrix metalloproteinase 9. In: Breast Cancer Research. 2008 ; Vol. 10, No. 5.
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abstract = "Introduction: Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed.Methods: We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR).Results: We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RT-PCR analysis of the index case.Conclusions: We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS.",
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AU - Cao, Dengfeng

AU - Polyak, Kornelia

AU - Halushka, Marc K.

AU - Nassar, Hind

AU - Kouprina, Nina

AU - Iacobuzio-Donahue, Christine

AU - Wu, Xinyan

AU - Sukumar, Saraswati

AU - Hicks, Jessica

AU - De Marzo, Angelo

AU - Argani, Pedram

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N2 - Introduction: Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed.Methods: We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR).Results: We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RT-PCR analysis of the index case.Conclusions: We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS.

AB - Introduction: Although lobular carcinoma in situ (LCIS) has traditionally been viewed as a marker of breast cancer risk, recent clinical, pathological and genetic analyses have supported the concept that LCIS is a low risk, direct precursor of invasive lobular carcinoma. Global gene expression profiling of LCIS has not been performed.Methods: We analysed the comprehensive gene expression profile of a unique case of mass-forming LCIS using serial analysis of gene expression (SAGE). This SAGE library is publicly available online. By comparing the gene expression profile of LCIS to that of benign breast epithelium and stroma, we identified several genes up and down regulated in LCIS. Differential expression of selected genes not previously studied in LCIS was validated at the protein level by immunohistochemistry and at the RNA level by quantitative reverse transcriptase PCR (RT-PCR).Results: We identified down regulation of claudin 4 and overexpression of matrix metalloproteinase 9 in LCIS relative to normal breast epithelium and stroma. We validated these findings by immunohistochemistry in a separate series of 11 and 19 LCIS cases, respectively. Overexpression of matrix metalloproteinase 9 was further confirmed by quantitative RT-PCR analysis of the index case.Conclusions: We have created the first global gene expression profile of LCIS, and demonstrated down regulation of cell junction proteins (an expected result) and overexpression of matrix metalloproteinase 9 (an unexpected result). Additional analysis of this data made available as an online resource should facilitate further molecular characterisation of LCIS.

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