Altered gene expression in breast cancer liver metastases

Rich66 · 01-09-2009, 06:42 AM

Nuray Erin^{1 2}, Ning Wang¹, Ping Xin¹, Voung Bui¹, Judith Weisz³, Gulisn Adkas-Barkan⁴, Wei Zhao⁵, Debra Shearer³, Gary A. Clawson^{1 6 *}

¹Departments of Pathology, Biochemistry and Molecular Biology, the Gittlen Cancer Research Foundation, Hershey Medical Center, Pennsylvania State University, Hershey, PA
²Department of Internal Medicine, Central Research Laboratory and Human Gene Therapy Unit, School of Medicine, Akdeniz University, Antalya, Turkey
³Department of Obstetrics and Gynecology, Hershey, Medical Center, Pennsylvania State University, Hershey, PA
⁴Department of Pathology, Loyola University Stritch School of Medicine, Maywood, IL
⁵Department of Health Evaluation Sciences, Hershey Medical Center, Pennsylvania State University, Hershey, PA
⁶College of Life Sciences and Technology, Southwest University for Nationalities of China, Chengdu, Sichuan, People's Republic of China

email: Gary A. Clawson (gac4@psu.edu)

^*Correspondence to Gary A. Clawson, Gittlen Cancer Research Foundation, C7768, H059, Hershey Medical Center, Pennsylvania State University, Hershey, PA 17033, USA
Funded by:

Gittlen Cancer Research Foundation, Akdeniz University

Pennsylvania Department of Health

Keywords

gene array • QPCR • immunocytochemistry • breast cancer • claudins • ZO-1 • liver metastases •

-catenin

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

-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

-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 -catenin, correlates with liver metastases, and that cell adhesion molecules in the microenvironment are also altered. © 2008 Wiley-Liss, Inc.

Rich66 · 01-09-2009, 06:43 AM

So..is it possible and would it help to elevate these proteins?