title: Beta protein 1 homeoprotein induces cell growth and estrogen-independent tumorigenesis by binding to the estrogen receptor in breast cancer.
abstract: Expression of Beta Protein 1 (BP1), a homeotic transcription factor, increases during breast cancer progression and may be associated with tumor aggressiveness. In our present work, we investigate the influence of BP1 on breast tumor formation and size in vitro and in vivo. Cells overexpressing BP1 showed higher viability when grown in the absence of serum (p < 0.05), greater invasive potential (p < 0.05) and formed larger colonies (p < 0.004) compared with the controls. To determine the influence of BP1 overexpression on tumor characteristics, MCF-7 cells transfected with either empty vector (V1) or overexpressor plasmids (O2 and O4) were injected into the fat pads of athymic nude mice. Tumors grew larger in mice receiving O2 or O4 cells than in mice receiving V1 cells. Moreover, BP1 mRNA expression levels were positively correlated with tumor size in patients (p = 0.01). Interestingly, 20% of mice injected with O2 or O4 cells developed tumors in the absence of estrogen, while no mice receiving V1 cells developed tumors. Several mechanisms of estrogen independent tumor formation related to BP1 were established. These data are consistent with the fact that expression of breast cancer anti-estrogen resistance 1 (BCAR1) was increased in O2 compared to V1 cells (p < 0.01). Importantly, O2 cells exhibited increased proliferation when treated with tamoxifen, while V1 cells showed growth inhibition. Overall, BP1 overexpresssion in MCF-7 breast cancer cells leads to increased cell growth, estrogen-independent tumor formation, and increased proliferation. These findings suggest that BP1 may be an important biomarker and therapeutic target in ER positive breast cancer.
authors.affiliation: Department of Medicine, Division of Genomic Medicine, George Washington University, Washington, DC 20037, USA.
authors.forename: Sidney W
authors.initials: SW
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC 20037, USA.
authors.forename: Saurabh P
authors.initials: SP
authors.lastname: Kirolikar
authors.affiliation: Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Ginsburg
authors.affiliation: Department of Medicine, Division of Genomic Medicine, George Washington University, Washington, DC 20037, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of Pathology, George Washington University Medical Center, Washington, DC 20037, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Schwartz
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health and Health Services, George Washington University, Washington, DC 20037, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Simmens
authors.affiliation: Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC 20306, USA.
authors.forename: Yan-Gao
authors.initials: YG
authors.lastname: Man
authors.affiliation: David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Pinzone
authors.affiliation: Department of Surgery, George Washington University, Washington, DC 20037, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Teal
authors.affiliation: Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC 20037, USA.
authors.forename: Sanket
authors.initials: S
authors.lastname: Awate
authors.affiliation: Mammary Biology and Tumorigenesis Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Vonderhaar
authors.affiliation: Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC 20037, USA.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Berg
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D008819:Mice, Nude; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics
chemical_list: C105304:DLX4 protein, human; D004967:Estrogens; D018398:Homeodomain Proteins; D011960:Receptors, Estrogen; D014157:Transcription Factors
keywords: BP1; estrogen receptor; homeobox gene; tamoxifen resistance; tumorigenesis