Determining whether cancer has spread to the lymph nodes is important in predicting survival from breast cancer and determining what treatment a patient requires. The traditional method of detecting such metastases, complete axillary node dissection, can result in lymphedema and other quality-of-life damaging side effects. The new technique of sentinel lymph node biopsy (SLNB) offers a way to test for lymph node metastases without causing the side effects of traditional axillary node dissection. Intraoperative analysis of SLNB is becoming an effective tool in assessment of the presence or absence of metastatic tumor, and therefore influences the treatment offered to the patient. Because of this central diagnostic use, as it is a new procedure, further studies need to be conducted to fully assess its role in breast cancer treatment.

Citation of original article:

S. Mukherjee, S. E. Conrad. Journal of Biological Chemistry 2005; 280: 17616–17625.

Abstract of the original article:

Oestrogen rapidly induces expression of the proto-oncogene c-Myc. c-Myc is required for oestrogen-stimulated proliferation of breast cancer cells, and deregulated c-Myc expression has been implicated in antioestrogen resistance. In this report, we investigate the mechanism(s) by which c-Myc mediates oestrogen-stimulated proliferation and contributes to cell cycle progression in the presence of antioestrogen. The MCF-7 cell line is a model of oestrogen-dependent, antioestrogen-sensitive human breast cancer. Using stable MCF-7 derivatives with inducible c-Myc expression, we demonstrated that in antioestrogen-treated cells, the elevated mRNA and protein levels of p21WAF1/CIP1, a cell cycle inhibitor, decreased upon either c-Myc induction or oestrogen treatment. Expression of p21 blocked c-Myc-mediated cell cycle progression in the presence of antioestrogen, suggesting that the decrease in p21WAF1/CIP1 is necessary for this process. Using RNA interference to suppress c-Myc expression, we further established that c-Myc is required for oestrogen-mediated decreases in p21WAF1/CIP1. Finally, we observed that neither c-Myc nor p21WAF1/CIP1 is regulated by oestrogen or antioestrogen in an antioestrogen-resistant MCF-7 derivative. The p21 levels in the antioestrogen-resistant cells increased when c-Myc expression was suppressed, suggesting that loss of p21 regulation was a consequence of constitutive c-Myc expression. Together, these studies implicate p21WAF1/CIP1 as an important target of c-Myc in breast cancer cells and provide a link between oestrogen, c-Myc, and the cell cycle machinery. They further suggest that aberrant c-Myc expression, which is frequently observed in human breast cancers, can contribute to antioestrogen resistance by altering p21WAF1/CIP1 regulation.