Matrix Metalloproteinase Expression Patterns in Luminal A Type Breast Carcinomas

Objective: Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters. Methods: The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT-PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement. Results: We observed high MMP2 levels more frequently in premenopausal than in postmenopausal women (p = 0.02). Analysis of luminal A type invasive ductal carcinomas (19/25), revealed an even stronger association of MMP2 with menopausal status (p = 0.005). Within this subgroup, we also found a correlation between MMP11 and menopausal status (p = 0.02). No correlation was found between MMP expressions and other clinicopathological parameters. In co-expression analyses MMP2-MMP10 and MMP8-MMP9 showed a weak correlation of their expression. Conclusions: Although this is a pilot study, our findings indicate that luminal A invasive ductal carcinomas commonly express high MMP2 and MMP11 levels in premenopausal breast cancer patients and suggest a co-regulation of MMP2-MMP10 and MMP8-MMP9.

[1]  C. Perou,et al.  Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. , 2006, JAMA.

[2]  J. Foidart,et al.  Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs in the respiratory tract: potential implications in asthma and other lung diseases. , 2006, European journal of pharmacology.

[3]  S. Katiyar.  Matrix metalloproteinases in cancer metastasis: molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyanidins. , 2006, Endocrine, metabolic & immune disorders drug targets.

[4]  X. Hao,et al.  [Clinical significance and relationship of expression of matrix metalloproteinase-2 mRNA with breast cancer metastasis]. , 2005, Zhonghua wai ke za zhi [Chinese journal of surgery].

[5]  T. Turpeenniemi‐Hujanen,et al.  Gelatinases (MMP-2 and -9) and their natural inhibitors as prognostic indicators in solid cancers. , 2005, Biochimie.

[6]  R. Ala-aho,et al.  Collagenases in cancer. , 2005, Biochimie.

[7]  V. Kosma,et al.  Expression of Matrix Metalloproteinase (MMP)-2 and MMP-9 in Breast Cancer with a Special Reference to Activator Protein-2, HER2, and Prognosis , 2004, Clinical Cancer Research.

[8]  N. Fusenig,et al.  Friends or foes — bipolar effects of the tumour stroma in cancer , 2004, Nature Reviews Cancer.

[9]  C. López-Otín,et al.  Matrix metalloproteinases in cancer: from new functions to improved inhibition strategies. , 2004, The International journal of developmental biology.

[10]  I. Pucci‐Minafra,et al.  Zymographic detection and clinical correlations of MMP-2 and MMP-9 in breast cancer sera , 2004, British Journal of Cancer.

[11]  L. Griffiths,et al.  An Assessment of MMP and TIMP Gene Expression in Cell Lines and Stroma – Tumour Differences in MicrodissectedBreast Cancer Biopsies , 2003, Tumor Biology.

[12]  Meirong Li,et al.  [Expression and clinical significance of MMP-2, MMP-9,TIMP-1, and TIMP-2 in breast carcinoma]. , 2003, Ai zheng = Aizheng = Chinese journal of cancer.

[13]  R. Tibshirani,et al.  Repeated observation of breast tumor subtypes in independent gene expression data sets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[14]  U. Sauer,et al.  Cellular Protein and mRNA Expression Patterns of Matrix Metalloproteinases-2, -3 and -9 in Human Breast Cancer: Correlation with Tumour Growth , 2003, Journal of Molecular Histology.

[15]  R. Tibshirani,et al.  Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[16]  M. Duffy,et al.  Metalloproteinases: role in breast carcinogenesis, invasion and metastasis , 2000, Breast Cancer Research.

[17]  C. Jackisch,et al.  Selection of potentially metastatic subpopulations expressing c-erbB-2 from breast cancer tissue by use of an extravasation model. , 1998, The American journal of pathology.

[18]  I. Nishimoto,et al.  Expression of gelatinases A and B, stromelysin-3 and matrilysin genes in breast carcinomas: clinico-pathological correlations , 1998, Clinical & Experimental Metastasis.

[19]  D. Gabard,et al.  Race , 1998, Encyclopedia of the UN Sustainable Development Goals.

[20]  B. Têtu,et al.  Prognostic significance of stromelysin 3, gelatinase A, and urokinase expression in breast cancer. , 1998, Human pathology.

[21]  D. Azar,et al.  Expression of gelatinases A and B, and TIMPs 1 and 2 during corneal wound healing. , 1998, Investigative ophthalmology & visual science.

[22]  R. Whitaker,et al.  Heregulin and agonistic anti-p185(c-erbB2) antibodies inhibit proliferation but increase invasiveness of breast cancer cells that overexpress p185(c-erbB2): increased invasiveness may contribute to poor prognosis. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[23]  Dihua Yu,et al.  Overexpression of the c-erbB-2 gene enhanced intrinsic metastasis potential in human breast cancer cells without increasing their transformation abilities. , 1997, Cancer research.

[24]  F. Ciardiello,et al.  Invasive phenotype of MCF10A cells overexpressing c‐Ha‐ras and c‐erbB‐2 oncogenes , 1995, International journal of cancer.

[25]  P. Neven,et al.  Plasma Gelatinase Levels in Patients with Primary Breast Cancer in Relation to Axillary Lymph Node Status, Her2/neu Expression and other Clinicopathological Variables , 2005, Clinical & Experimental Metastasis.

[26]  S. Zucker,et al.  Role of matrix metalloproteinases (MMPs) in colorectal cancer , 2004, Cancer and Metastasis Reviews.