"Methods of diagnosis, prognosis and treating breast cancer."

The protein pRb2/p130 represses expression of the ER-.alpha. gene. Blocking pRb2/p130 expression or altering ER-.alpha. gene methylation to alter pRb2/p130 complex binding allows transcriptional activity of the ER-.alpha. gene to be restored. Detecting and regulating the methylation state of the ER-.alpha. gene, optionally together with detecting and regulating pRb2/p130 multimolecular complexes bound to the ER-.alpha. gene promoter, allows estrogen-insensitive breast cancer cells to be identified, so that an accurate prognosis can be obtained and an appropriate course of treatment administered. Also, inhibiting pRb2/p130, or altering the methylation pattern of the ER-.alpha. gene by targeting DNMT 1 I n the pRb2/p 130-E2F4/5-HDAC 1-DNMT1-SUV39H1 complex, allows estrogen-insensitive breast cancer cells to be converted to estrogen-sensitive breast cancer cells. Estrogen-sensitive breast cancer cells which are generally more susceptible to current anti-cancer treatments.