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, Robert L. Shepard, Xiaoling Xia, Viswanath Devanarayan, George Sandusky, William L. Perry, Anne H. Dantzig, Mark Williamson, Mark Rolfe, Robert E. Moore

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1781-1790
Number of pages10
JournalAmerican Journal of Pathology
Volume163
Issue number5
StatePublished - Nov 2003
Externally publishedYes

Fingerprint

Phenotype
Alternative Splicing
Drug Resistance
Prostate
Neoplasms
Breast
Tissue Array Analysis
Spliceosomes
Carcinoma
Vincristine
Pharmaceutical Preparations
Doxorubicin
Cyclophosphamide
Pancreas
Colon
Urinary Bladder
Epithelial Cells
Breast Neoplasms
Cell Line
Lung

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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. / Sampath, Janardhan; Long, Pandy R.; Shepard, Robert L.; Xia, Xiaoling; Devanarayan, Viswanath; Sandusky, George; Perry, William L.; Dantzig, Anne H.; Williamson, Mark; Rolfe, Mark; Moore, Robert E.

In: American Journal of Pathology, Vol. 163, No. 5, 11.2003, p. 1781-1790.

Research output: Contribution to journalArticle

Sampath, J, Long, PR, Shepard, RL, Xia, X, Devanarayan, V, Sandusky, G, Perry, WL, Dantzig, AH, Williamson, M, Rolfe, M & Moore, RE 2003, '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', American Journal of Pathology, vol. 163, no. 5, pp. 1781-1790.
Sampath, Janardhan ; Long, Pandy R. ; Shepard, Robert L. ; Xia, Xiaoling ; Devanarayan, Viswanath ; Sandusky, George ; Perry, William L. ; Dantzig, Anne H. ; Williamson, Mark ; Rolfe, Mark ; Moore, Robert E. / 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. In: American Journal of Pathology. 2003 ; Vol. 163, No. 5. pp. 1781-1790.
@article{3ee16c3c471e4dd889282bfa32efee44,
title = "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",
abstract = "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.",
author = "Janardhan Sampath and Long, {Pandy R.} and Shepard, {Robert L.} and Xiaoling Xia and Viswanath Devanarayan and George Sandusky and Perry, {William L.} and Dantzig, {Anne H.} and Mark Williamson and Mark Rolfe and Moore, {Robert E.}",
year = "2003",
month = "11",
language = "English (US)",
volume = "163",
pages = "1781--1790",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - 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

AU - Sampath, Janardhan

AU - Long, Pandy R.

AU - Shepard, Robert L.

AU - Xia, Xiaoling

AU - Devanarayan, Viswanath

AU - Sandusky, George

AU - Perry, William L.

AU - Dantzig, Anne H.

AU - Williamson, Mark

AU - Rolfe, Mark

AU - Moore, Robert E.

PY - 2003/11

Y1 - 2003/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0142182109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142182109&partnerID=8YFLogxK

M3 - Article

VL - 163

SP - 1781

EP - 1790

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 5

ER -