HMG-I/Y in human breast cancer cell lines.
The HMG-I/Y gene encodes the HMG-I and -Y architectural, chromatin binding proteins originally identified based on their association with chromosomal DNA. HMG-I/Y proteins bind to AT-rich regions in chromosomal DNA and alter gene expression. Increased HMG-I/Y protein expression also correlates with neoplastic transformation. Previous work from our laboratory has shown that HMG-I/Y is a direct c-Myc target gene involved in neoplastic transformation in Burkitt's lymphoma. We also observed that HMG-I/Y proteins have several oncogenic properties. In this report, we show that HMG-I/Y proteins are increased in several human breast cancer cell lines compared to a human breast cell line derived from normal breast cells. Decreasing HMG-I/Y proteins using an antisense ribozyme approach inhibits transformation in human breast cancer cells, suggesting that HMG-I/Y is important for the transformed phenotype observed in these cells. In addition, increased expression of the HMG-I isoform in normal human breast cells leads to transformation. These results suggest that HMG-I/Y is an oncogene important in the pathogenesis of human breast cancer. Although additional studies with animal models are needed, the antisense experiments, which result in blocking transformation suggest that this approach may have therapeutic potential in patients with breast cancer characterized by increased HMG-I/Y expression.
Dolde
Christine E
CE
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mukherjee
Mita
M
Cho
Chung
C
Resar
Linda M S
LM
D015153:Blotting, Western; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D025741:HMGA1a Protein / Q000235:genetics*; D006801:Humans; D014407:Tumor Cells, Cultured
D025741:HMGA1a Protein