Human leukocyte antigen G expression in breast cancer: role in immunosuppression.

Human leukocyte antigen G (HLA-G) is an immunotolerant nonclassical major histocompatibility complex Class Ib molecule. It is expressed by trophoblastic placental cells during pregnancy to protect the fetus from maternal alloreactivity. HLA-G is overexpressed in tumors and involved in cancer immune evasion.

Manipulation of iron transporter genes results in the suppression of human and mouse mammary adenocarcinomas.

Since malignant cells often have a high demand for iron, we hypothesize that breast cancer cells may alter the expression of iron transporter genes including iron importers [transferrin receptor (TFRC) and solute carrier family 11 (proton-coupled divalent metal ion transporters), member 2 (SLC11A2)] and the iron exporter SLC40A1 (ferroportin), and additionally that the growth of breast cancer can be inhibited by manipulating iron transporter gene expression. To test our hypothesis, reverse transcription polymerase chain reaction (RT-PCR) was used to determine mRNA expression of iron transporter genes in normal human mammary epithelial MCF-12A cells and human breast cancer MCF-7 cells. Antisense oligonucleotides were employed to suppress the expression of TFRC gene in the 4T1 mammary adenocarcinoma in both cell culture and a mouse tumor model.

Induction of apoptosis by iron depletion in the human breast cancer MCF-7 cell line and the 13762NF rat mammary adenocarcinoma in vivo.

It is known that the interruption of normal iron metabolism with chelators of iron, toxic metals, toxic metals bound to transferrin, or anti-transferrin receptor antibodies leads to significant inhibition of tumor cell growth in cell culture systems and animal models. In the present study, we found that iron depletion was produced by the iron chelator deferoxamine mesylate, the free toxic metals gallium or indium, and the toxic metals gallium or indium bound to transferrin in the MCF-7 human breast cancer cell line, and this induced the condensation and fragmentation of chromatin, and the formation of DNA fragments characteristic of apoptosis. The induction of apoptosis was quantitated with acridine orange and ethidium bromide staining of apoptotic cells, separation of fragmented DNA from radiolabeled cells, and in situ terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assays.