title: Expression of estrogen receptor alpha with a Tet-off adenoviral system induces G0/G1 cell cycle arrest in SKBr3 breast cancer cells.
abstract: Endocrine therapies targeting estrogen action are pivotal for the prevention and treatment of ER-positive breast cancers. Previous studies sought to recreate hormone responsiveness by the stable expression of ERalpha in the ER-negative MDA-MB-231 breast cancer cells. Paradoxically, estrogen inhibits breast cancer cell growth when an exogenous ERalpha is expressed. In this study, we have built on previous studies by developing a Tet-off adenoviral system to express ERalpha in the ER-negative SKBr3 breast cancer cells that over-express both EGFR and HER2. This system efficiently delivers ERalpha and the expression level of ERalpha is controlled by doxycycline in a concentration-dependent manner. The growth of SKBr3 was inhibited by ERalpha expression and further inhibited in the presence of 1 nM 17beta-estradiol. SKBr3 cells were arrested at G0/G1 cell cycle upon ERalpha expression, which corresponded to an increase of p21Cip1/Waf1, hypo-phosphorylation of pRb and decrease of E2F1. Estrogen also reduced EGFR and HER2 expression in SKBr3 cells after ERalpha was expressed. Given that estrogen-induced increase of p21Cip1/Waf1 and decrease of E2F1 was also observed in MDA-MB-231 cells stably transfected with ERalpha, our results suggest that a common pathway might be shared by different breast cancer cell lines whose growth is suppressed by ectopic ERalpha and estrogen.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.forename: V Craig
authors.initials: VC
authors.lastname: Jordan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013753:Tetracycline Resistance / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D004967:Estrogens; D018719:Erb-b2 Receptor Tyrosine Kinases; C493753:E2F1 protein, human