Wulf Gerburg, Ryo Akihide, Liou Yih-Cherng, Lu Kun Ping
Cancer Biology Program, Division of Hematology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Breast Cancer Res. 2003;5(2):76-82. doi: 10.1186/bcr572. Epub 2003 Jan 28.
The prolyl isomerase Pin1 specifically isomerizes certain phosphorylated Ser/Thr-Pro bonds and thereby regulates various cellular processes. Pin1 is a target of several oncogenic pathways and is overexpressed in human breast cancer. Its overexpression can lead to upregulation of cyclin D1 and transformation of breast epithelial cells in collaboration with the oncogenic pathways. In contrast, inhibition of Pin1 can suppress the transformation of breast epithelial cells. In addition, Pin1 knockout in mice prevents massive proliferation of breast epithelial cells during pregnancy. Pin1 plays a pivotal role in breast development and may be a promising new anticancer target.
脯氨酰异构酶Pin1特异性地使某些磷酸化的丝氨酸/苏氨酸-脯氨酸键发生异构化，从而调节各种细胞过程。Pin1是多种致癌途径的靶点，在人类乳腺癌中过表达。其过表达可导致细胞周期蛋白D1上调，并与致癌途径协同作用使乳腺上皮细胞发生转化。相反，抑制Pin1可抑制乳腺上皮细胞的转化。此外，小鼠中Pin1基因敲除可防止孕期乳腺上皮细胞的大量增殖。Pin1在乳腺发育中起关键作用，可能是一个有前景的新抗癌靶点。
