The present study found that Shp2 formed a complex with receptors of estrogen near cytoplasmic membrane responding to estrogen stimulation, and then transduced the estrogen signal by triggering the cytoplasmic pathways ERK and AKT to induce gene transcription (such as Cyclin D1 and TFF1), DNA synthesis, and cell proliferation in breast cancer cells. The gene discussed is CCND1; the disease is breast cancer.