Altered gene expression in breast cancer liver metastases

Nuray Erin, Ning Wang, Ping Xin, Voung Bui, Judith Weisz, Guliz A. Barkan, Wei Zhao, Debra Shearer, Gary Clawson

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We previously developed a highly aggressive cell line from heart metastases of 4T1 breast carcinoma (designated 4THM), which produced liver metastases (designated 4TLM). In this study, gene array analysis (GAEA) compared gene expression profiles in 4TLM with profiles in 4T1 and 4THM primary tumors. GAEA demonstrated that 4T1 and 4THM tumors differed in about 250 genes. Over 1,000 genes, however, were expressed differently in 4TLM compared with primary tumors. A cohort of 16 genes showed significantly decreased expression in 4THM tumors, which decreased even further in 4TLM. Many of these genes have been implicated in breast cancer, and many are involved in cell adhesion and junctional complexes. Expression of multiple tight and adherence junction proteins was either downregulated or disappeared in 4TLM; downregulation of claudin 4, claudin 7 and y- catenin was confirmed by quantitative polymerase chain reaction, immunoblot, and immunocytochemical (ICC) analyses. At the protein level, intact ZO-1 was also observed in 4T1 tumors, but was not expressed in 4THM or 4TLM tumors. ICC demonstrated expression of y-catenin at the plasma membrane with 4T1 tumors, whereas staining appeared to be nuclear/perinuclear in 4THM tumors. Claudin 7 staining was also seen in monocyte/pmacrophage-like cells in liver around metastatic lesions by ICC, and it appeared that larger 4TLM tumors apparently reexpressed claudin 7 RNA and protein. Our results demonstrate that decreased or abnormal expression of a number of cell adhesion/junctional proteins, including claudin 4, 7, ZO-1 and y-catenin, correlates with liver metastases, and that cell adhesion molecules in the microenvironment are also altered.

Original languageEnglish (US)
Pages (from-to)1503-1516
Number of pages14
JournalInternational Journal of Cancer
Volume124
Issue number7
DOIs
StatePublished - Apr 1 2009

Fingerprint

Liver Neoplasms
Breast Neoplasms
Neoplasm Metastasis
Gene Expression
Catenins
Neoplasms
Claudin-4
Genes
Cell Adhesion
Down-Regulation
Staining and Labeling
Tight Junction Proteins
Proteins
Liver
Cadherins
Transcriptome
Monocytes
Cell Membrane
RNA
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Erin, Nuray ; Wang, Ning ; Xin, Ping ; Bui, Voung ; Weisz, Judith ; Barkan, Guliz A. ; Zhao, Wei ; Shearer, Debra ; Clawson, Gary. / Altered gene expression in breast cancer liver metastases. In: International Journal of Cancer. 2009 ; Vol. 124, No. 7. pp. 1503-1516.
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abstract = "We previously developed a highly aggressive cell line from heart metastases of 4T1 breast carcinoma (designated 4THM), which produced liver metastases (designated 4TLM). In this study, gene array analysis (GAEA) compared gene expression profiles in 4TLM with profiles in 4T1 and 4THM primary tumors. GAEA demonstrated that 4T1 and 4THM tumors differed in about 250 genes. Over 1,000 genes, however, were expressed differently in 4TLM compared with primary tumors. A cohort of 16 genes showed significantly decreased expression in 4THM tumors, which decreased even further in 4TLM. Many of these genes have been implicated in breast cancer, and many are involved in cell adhesion and junctional complexes. Expression of multiple tight and adherence junction proteins was either downregulated or disappeared in 4TLM; downregulation of claudin 4, claudin 7 and y- catenin was confirmed by quantitative polymerase chain reaction, immunoblot, and immunocytochemical (ICC) analyses. At the protein level, intact ZO-1 was also observed in 4T1 tumors, but was not expressed in 4THM or 4TLM tumors. ICC demonstrated expression of y-catenin at the plasma membrane with 4T1 tumors, whereas staining appeared to be nuclear/perinuclear in 4THM tumors. Claudin 7 staining was also seen in monocyte/pmacrophage-like cells in liver around metastatic lesions by ICC, and it appeared that larger 4TLM tumors apparently reexpressed claudin 7 RNA and protein. Our results demonstrate that decreased or abnormal expression of a number of cell adhesion/junctional proteins, including claudin 4, 7, ZO-1 and y-catenin, correlates with liver metastases, and that cell adhesion molecules in the microenvironment are also altered.",
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Erin, N, Wang, N, Xin, P, Bui, V, Weisz, J, Barkan, GA, Zhao, W, Shearer, D & Clawson, G 2009, 'Altered gene expression in breast cancer liver metastases', International Journal of Cancer, vol. 124, no. 7, pp. 1503-1516. https://doi.org/10.1002/ijc.24131

Altered gene expression in breast cancer liver metastases. / Erin, Nuray; Wang, Ning; Xin, Ping; Bui, Voung; Weisz, Judith; Barkan, Guliz A.; Zhao, Wei; Shearer, Debra; Clawson, Gary.

In: International Journal of Cancer, Vol. 124, No. 7, 01.04.2009, p. 1503-1516.

Research output: Contribution to journalArticle

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AU - Erin, Nuray

AU - Wang, Ning

AU - Xin, Ping

AU - Bui, Voung

AU - Weisz, Judith

AU - Barkan, Guliz A.

AU - Zhao, Wei

AU - Shearer, Debra

AU - Clawson, Gary

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