help button home button Am J Pathol Epitomics
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sampath, J.
Right arrow Articles by Moore, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sampath, J.
Right arrow Articles by Moore, R. E.
(American Journal of Pathology. 2003;163:1781-1790.)
© 2003 American Society for Investigative Pathology

Human SPF45, a Splicing Factor, Has Limited Expression in Normal Tissues, Is Overexpressed in Many Tumors, and Can Confer a Multidrug-Resistant Phenotype to Cells

Janardhan Sampath*, Pandy R. Long{dagger}, Robert L. Shepard*, Xiaoling Xia*, Viswanath Devanarayan{ddagger}, George E. Sandusky{dagger}, William L. Perry, III*, Anne H. Dantzig*, Mark Williamson§, Mark Rolfe§ and Robert E. Moore*

From the Cancer Research Division,*the Molecular Pathology Division of Bio-Research Technologies and Proteins,{dagger}and the Global Discovery and Development Statistics,{ddagger}Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana; and Millennium Pharmaceuticals,§Boston, Massachusetts

Our effort to identify novel drug-resistant genes in cyclophosphamide-resistant EMT6 mouse mammary tumors led us to the identification of SPF45. Simultaneously, other groups identified SPF45 as a component of the spliceosome that is involved in alternative splicing. We isolated the human homologue and examined the normal human tissue expression, tumor expression, and the phenotype caused by overexpression of human SPF45. Our analyses revealed that SPF45 is expressed in many, but not all, normal tissues tested with predominant expression in normal ductal epithelial cells of the breast, liver, pancreas, and prostate. Our analyses using tissue microarrays and sausages of tumors indicated that SPF45 is highly expressed in numerous carcinomas including bladder, breast, colon, lung, ovarian, pancreatic, and prostate. Interestingly, this study revealed that overexpression of SPF45 in HeLa, a cervical carcinoma cell line, resulted in drug resistance to doxorubicin and vincristine, two chemotherapeutic drugs commonly used in cancer. To our knowledge, this is the first study showing tumor overexpression of an alternate splicing factor resulting in drug resistance.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
M. Korner and L. J. Miller
Alternative Splicing of Pre-mRNA in Cancer: Focus on G Protein-Coupled Peptide Hormone Receptors
Am. J. Pathol., August 1, 2009; 175(2): 461 - 472.
[Abstract] [Full Text] [PDF]

Home page
 Genome ResHome page
V. Bansal, A. Bashir, and V. Bafna
Evidence for large inversion polymorphisms in the human genome from HapMap data
Genome Res., February 1, 2007; 17(2): 219 - 230.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
W. L. Perry III, R. L. Shepard, J. Sampath, B. Yaden, W. W. Chin, P. W. Iversen, S. Jin, A. Lesoon, K. A. O'Brien, V. L. Peek, et al.
Human Splicing Factor SPF45 (RBM17) Confers Broad Multidrug Resistance to Anticancer Drugs When Overexpressed-- a Phenotype Partially Reversed By Selective Estrogen Receptor Modulators
Cancer Res., August 1, 2005; 65(15): 6593 - 6600.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
C. L. Kielkopf, S. Lucke, and M. R. Green
U2AF homology motifs: protein recognition in the RRM world
Genes & Dev., July 1, 2004; 18(13): 1513 - 1526.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.