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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Human SPF45, a splicing factor, has limited expression in normal tissues, is overexpressed in many tumors, and can

Janardhan Sampath1, Pandy R Long, Robert L Shepard

  • 1Cancer Research Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.

The American Journal of Pathology
|October 28, 2003
PubMed

Insights

Scientists identified SPF45, a spliceosome component, as a factor in cancer drug resistance. Overexpression of SPF45 in tumors and cell lines correlated with resistance to common chemotherapy drugs.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cyclophosphamide resistance in EMT6 mouse mammary tumors prompted the search for novel drug-resistant genes.
  • SPF45 was concurrently identified by other researchers as a spliceosome component involved in alternative splicing.

Purpose of the Study:

  • To investigate the role of SPF45 in cancer drug resistance.
  • To examine the expression pattern of human SPF45 in normal and cancerous tissues.
  • To determine the phenotypic effects of SPF45 overexpression in cancer cells.

Main Methods:

  • Identification of SPF45 in drug-resistant mouse tumors.
  • Isolation and analysis of the human SPF45 homologue.
  • Assessment of SPF45 expression in normal human tissues and various carcinomas using tissue microarrays.
  • Overexpression studies of SPF45 in HeLa cervical carcinoma cells.

Main Results:

  • SPF45 is expressed in various normal human tissues, notably ductal epithelial cells of the breast, liver, pancreas, and prostate.
  • High SPF45 expression was observed in multiple carcinomas, including bladder, breast, colon, lung, ovarian, pancreatic, and prostate cancers.
  • Overexpression of SPF45 in HeLa cells conferred resistance to doxorubicin and vincristine chemotherapy.

Conclusions:

  • SPF45 is a frequently overexpressed splicing factor in numerous human carcinomas.
  • Tumor overexpression of SPF45 is linked to acquired resistance to common chemotherapeutic agents.
  • This study presents the first evidence of an alternative splicing factor contributing to tumor drug resistance.

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