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Overexpression of Oncogenic STK15/BTAK/Aurora A Kinase in Human Pancreatic Cancer¹

Departments of Gastrointestinal Medical Oncology [D. L., J. Z., P. F. F., J. L. A.], Surgical Oncology [D. B. E.], Pathology [K. C.], and Molecular Pathology [S. S.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and University of Bern, Inselspital, Bern, Switzerland [H. F.]

Purpose: Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer.

Experimental Design: STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry.

Results: STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2–10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors.

Conclusions: These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis.

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