Treatment of breast cancer cells with proteasome inhibitor lactacystin increases the level of sensitivity to cell death induced by human immunodeficiency virus type 1.
Upon binding to CD4, the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 undergoes conformational changes that facilitate subsequent interactions with the chemokine coreceptor CXCR4 on the T cells. Our previous study showed that HIV-1 induces breast cancer cell death through gp120-CXCR4 interaction without CD4-induced conformational change of gp120. To characterize the structural properties of CXCR4 on breast cancer cells, the structural differences in CXCR4 between breast cancer cell lines and T cells were investigated. Immunoblots of whole cell lysates from breast cancer cell and T cell lines demonstrated that the predominant forms of CXCR4 on the breast cancer cell lines and T cell lines were three species (45, 61, 100 kDa) and one species (45 kDa), respectively. Cell surface biotin labeling revealed that the 100-kDa polyubiquitinated form of CXCR4 is specifically expressed on the surface of breast cancer cell line DU4475 but not T cell line Molt4#8. The treatment of breast cancer cell lines MDA-MB231 and DU4475 with proteasome inhibitor lactacystin leads to increased surface expression of the 100-kDa polyubiquitinated form of CXCR4 and increases the level of sensitivity to cell death induced by HIV-1. These data suggest that the 100-kDa polyubiquitinated form of CXCR4 plays an important role as a trigger for gp120-induced breast cancer cell death.
Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5–1 Oe-honmachi, Kumamoto 862–0973, Japan.
Masafumi
M
Endo
Shouichirou
S
Gejima
Asako
A
Endo
Nobutoki
N
Takamune
Shozo
S
Shoji
Shogo
S
Misumi
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications* / Q000503:physiopathology / Q000821:virology; D015497:HIV-1; D006801:Humans; D025821:Polyubiquitin / Q000378:metabolism; D061988:Proteasome Inhibitors; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D015699:HIV Envelope Protein gp120; D061988:Proteasome Inhibitors; D019718:Receptors, CXCR4; D025821:Polyubiquitin; C067713:lactacystin; D000111:Acetylcysteine