Bcl-2-related antisense therapy.
High expression of the bcl-2 proto-oncogene is found in various human hematologic malignancies and solid tumors. Bcl-2 protein exerts its oncogenic role by preventing tumor cells from undergoing apoptosis induced by radiation, chemotherapy, and hormonal therapy. Antisense oligonucleotides directed toward the open reading frame of the bcl-2 gene have been used to inhibit Bcl-2 expression. Inhibition of Bcl-2 expression sensitizes lymphoma and leukemia cells to radiation and chemotherapy. However, it remains to be determined whether Bcl-2 antisense oligonucleotides will have a beneficial effect in solid tumors, such as breast cancer. Laboratory results indicate that Bcl-2 overexpression induces endocrine and chemoresistance in breast cancer cells. However, high levels of Bcl-2 have been associated with favorable prognostic factors, suggesting that Bcl-2 may not be an appropriate target in breast cancer. We will discuss the paradoxical role of Bcl-2 and the potential therapeutic application of Bcl-2 antisense oligonucleotides in breast cancer.
Gutiérrez-Puente
Yolanda
Y
Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, Monterrey, N.L., México.
Zapata-Benavides
Pablo
P
Tari
Ana M
AM
López-Berestein
Gabriel
G
D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*
C000715470:MAS1 protein, human; D020319:Oligodeoxyribonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2