Modification of survival pathway gene expression in human breast cancer cells by tetraiodothyroacetic acid (tetrac).
Tetraiodothyroacetic acid (tetrac) inhibits the cellular actions of thyroid hormone initiated at the hormone receptor on plasma membrane integrin alphavbeta3. Via interaction with the integrin, tetrac is also capable of inhibiting the angiogenic effects of vascular endothelial growth factor and basic fibroblast growth factor. MDA-MB-231 cells are estrogen receptor-negative human breast cancer cells shown to be responsive to tetrac in terms of decreased cell proliferation. Here we describe actions initiated at the cell surface receptor by unmodified tetrac and nanoparticulate tetrac on a panel of survival pathway genes in estrogen receptor-negative human breast cancer (MDA-MB-231) cells. Nanoparticulate tetrac is excluded from the cell interior. Expression of apoptosis inhibitors XIAP (X-linked inhibitor of apoptosis) and MCL1 (myeloid cell leukemia sequence 1) was downregulated by nanoparticulate tetrac in these breast cancer cells whereas apoptosis-promoting CASP2 and BCL2L14 were upregulated by the nanoparticulate formulation. Unmodified tetrac affected only XIAP expression. Expression of the angiogenesis inhibitor thrombospondin 1 (THBS1) gene was increased by both formulations of tetrac, as was the expression of CBY1, a nuclear inhibitor of catenin activity. The majority of differentially regulated Ras-oncogene family members were downregulated by nanoparticulate tetrac. The latter downregulated expression of epidermal growth factor receptor gene and unmodified tetrac did not. Nanoparticulate tetrac has coherent anti-cancer actions on expression of differentially-regulated genes important to survival of MDA-MB-231 cells.
Glinskii
Anna B
AB
Ordway Research Institute, Albany College of Pharmacy, Albany, NY, USA.
Glinsky
Gennadi V
GV
Lin
Hung-Yun
HY
Tang
Heng-Yuan
HY
Sun
Mingzeng
M
Davis
Faith B
FB
Luidens
Mary K
MK
Mousa
Shaker A
SA
Hercbergs
Aleck H
AH
Davis
Paul J
PJ
D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000819:agonists / Q000378:metabolism; D053143:Caspase 2 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D011905:Genes, ras / Q000187:drug effects / Q000502:physiology; D006801:Humans; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D053758:Nanoparticles; D009687:Nuclear Proteins / Q000819:agonists / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019700:Thrombospondin 1 / Q000819:agonists / Q000378:metabolism; D013974:Thyroxine / Q000031:analogs & derivatives / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
C428448:BCL2L14 protein, human; C473750:CBY1 protein, human; D002352:Carrier Proteins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D005346:Fibroblast Growth Factors; C490360:CASP2 protein, human; D053143:Caspase 2; D003546:Cysteine Endopeptidases; C011126:tetraiodothyroacetic acid; D013974:Thyroxine