Published online before print September 14, 2007

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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.070325

Accepted for publication August 3, 2007.

Article

Myosin II Co-Chaperone General Cell UNC-45 Overexpression Is Associated with Ovarian Cancer, Rapid Proliferation, and Motility

Martina Bazzaro^*, Antonio Santillan^*, Zhenhua Lin^*, Taylor Tang^*, Michael K. Lee^*, Robert E. Bristow^¶, Ie-Ming Shih^*¶, and Richard B.S. Roden^*¶@

From the Departments of Pathology,* Oncology,^¶ Gynecology and Obstetrics, The Johns Hopkins School of Medicine, Baltimore, Maryland; the Department of Pathology, Yanbian University College of Medicine, and the Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education, Yanji-City, People's Republic of China

^@ To whom correspondence should be addressed. E-mail: roden{at}jhmi.edu.

	Abstract

Both tumor cell proliferation and metastasis are dependent on myosin II. Because UNC-45 is required to chaperone the assembly of a functional myosin II motor, we examined the expression of the general cell (GC) UNC-45 isoform in ovarian tumors. Serous carcinoma expressed elevated levels of GC UNC-45 compared with normal ovarian surface epithelium and benign cystadenoma. High-stage exhibited greater GC UNC-45 expression than low-stage serous carcinoma. Similarly, GC UNC-45 transcripts and protein levels were higher in ovarian cell lines than in immortalized ovarian surface epithelial cells. Elevation of GC UNC-45 levels by ectopic expression enhanced the rate of ovarian cancer cell proliferation, whereas siRNA knockdown of GC UNC-45 suppressed proliferation without altering myosin II levels. GC UNC-45 and myosin II were diffuse within the cytoplasm of confluent interphase cells, but both accumulated together at the cleavage furrow during cytokinesis. GC UNC-45 and myosin II also trafficked to the leading edges of ovarian cancer cells induced to move in a scratch assay. Knockdown of GC UNC-45 reduced the spreading ability of ovarian cancer cells whereas it was enhanced by GC UNC-45 overexpression. In sum, these findings implicate elevated GC UNC-45 protein expression in ovarian carcinoma proliferation and metastasis.