|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Cell Biology International (1998) 22, 413419 (Printed in Great Britain)
A METASTATIC BREAST TUMOR CELL LINE, GI-101A, IS ESTROGEN RECEPTOR POSITIVE AND RESPONSIVE TO ESTROGEN BUT RESISTANT TO TAMOXIFEN
JOSEPH J. MORRISSEYaf1 and SHULA RANEYb
aMotorola Biological Research Program, Ft. Lauderdale, FL, 33322, U.S.A.
bGoodwin Biotechnology Institute, Ft. Lauderdale, FL, 33322, U.S.A.
The progression of human breast cancer is often associated with a loss of estrogen dependence for growth, a resistance to estrogen antagonists such as tamoxifen, and the metastatic spread of the disease to secondary sites. Cell lines developed from such advanced breast tumors are often metastatic in athymic mice, show a loss of estrogen receptor mRNA and protein (ER−), and do not respond to 17β-estradiol. However many advanced human breast tumors do express significant amounts of ER transcript, especially when analyzed by more sensitive methods of detection including RT-PCR and Ribonuclease Protection Assay (RPA). No metastatic, ER+breast tumor cell line has previously existed to examine the role of ER in metastatic progression and acquired drug (tamoxifen) resistance. The GI-101A cell line was recently developed from a metastatic breast tumor xenograft and is both tumorogenic and metastatic to the lungs and lymph node when injected into athymic mice, a pattern similar to that seen in patients. While Western blot analysis initially indicated that GI-101A was ER−, analysis of ER mRNA by RT-PCR and RPA have demonstrated the expression of ER (as well as EGF receptor andneuoncogene) transcripts. Functional ER in GI-101A was confirmed by a clear growth response to 17β-estradiol in culture. Optimal 17β-estradiol concentrations were significantly lower for GI101A than for MCF-7 (1
Key words: breast cancer, metastasis, estrogen receptor, tamoxifen resistance, alternate splicing.
f1To whom correspondence should be addressed.
Received 26 October 1997; accepted 22 May 1998doi:10.1006/cbir.1998.0269