CAML promotes prolactin-dependent proliferation of breast cancer cells by facilitating prolactin receptor signaling pathways.
Calcium-modulating cyclophilin ligand (CAML) interacts with the intracellular regions of various types of membrane-bound receptors, and is required for signaling pathways that involve these receptors. The authors tested the possibility that CAML interacts with prolactin receptor (PRLR) and participates in the prolactin (PRL)-dependent proliferation of breast cancer cells. Breast cancer cell lines were found to express CAML at higher levels than cell lines originating from leukemia and other cancers. Furthermore, immunohistochemical analyses of breast tissue arrays showed that the CAML levels were higher in cancer tissues than in normal tissues. In breast cancer cells and transfected HEK293 cells, CAML associated with PRLR, and this interaction was augmented during PRL stimulation. CAML-silencing experiments revealed that CAML is required for the functions of PRLR, such as, the activations of Stat5 and Mek1/2, PRL internalization with cyclophilin B, PRLR recycling, and increased Ca(2+) mobilization. In addition, CAML was found to play a crucial role in the PRL/PRLR-dependent growth of breast cancer cells. These results suggest a new role for CAML in breast cancer development.
Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul, 110-799, Korea.
Ji-hong
JH
Lim
Tae-you
TY
Kim
Woo-ho
WH
Kim
Jong-wan
JW
Park
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008875:Middle Aged; D011388:Prolactin / Q000378:metabolism*; D011485:Protein Binding; D011981:Receptors, Prolactin / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; C089404:CAMLG protein, human; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D011388:Prolactin