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 language | English (US) |
|---|---|
| Pages (from-to) | 1781-1790 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 163 |
| Issue number | 5 |
| State | Published - Nov 2003 |
| Externally published | Yes |
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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 journal › Article
}
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
C2 - 14578179
AN - SCOPUS:0142182109
VL - 163
SP - 1781
EP - 1790
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 5
ER -