Differential expression of alternatively spliced c-erbB-2 mRNA in primary tumors, lymph node metastases, and bone marrow micrometastases from breast cancer patients

Biochemical and Biophysical Research Communications
F GebhardtB Brandt

Abstract

We established an RT-PCR method to measure the amount of a 2.3-kb alternatively spliced mRNA of the human c-erbB-2/HER-2 proto-oncogene relative to the 4.6-kb full-length transcript. For the first time, we demonstrated production of c-erbB-2 extracellular domains via alternative splicing in breast cancer tissues, lymph node and bone marrow micrometastases. In 15 c-erbB-2-positive primary breast tumor samples, we found two significantly distinct subgroups: 6/15 had a low level of the extracellular fragment, and 9/15 showed an average 4.4-fold higher amount of the alternatively spliced mRNA. Additionally, six lymph nodes and six bone marrow aspirates from metastatic breast cancer patients were analyzed: 5/6 lymph nodes and 6/6 bone marrow aspirates were found to produce elevated relative amounts of the truncated fragment. The results demonstrate that our method is suitable for sensitive detection of c-erbB-2-positive micrometastasis and strongly suggest that the alternatively spliced c-erbB-2 variant is involved in the development of micrometastasis in breast cancer.

Citations

Aug 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Adam P Dicker, Ulrich Rodeck
Feb 28, 2002·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Cleanthi DimasA Kondis-Pafitis
May 23, 2002·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Shinichi TsutsuiYoichi Hachitanda
Dec 15, 2000·Oncogene·W LinH C Chen
Apr 12, 2000·Cancer Control : Journal of the Moffitt Cancer Center·E A Perez
Sep 25, 2002·Critical Reviews in Oncology/hematology·R S RampaulI O Ellis

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