High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes

Maria E. Gonzalez, Esther A. Peterson, Lisa M. Privette, Janice L. Loffreda-Wren, Linda M. Kalikin, Elizabeth M. Petty

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Abstract

Altered expression of the human septin gene, SEPT9, and its murine homologue, Sept9, has been implicated in neoplasia. However, their role(s) in oncogenesis remains poorly understood. We found amplification of SEPT9 in 67% of breast cancer cells (BCC) when compared with immortalized human mammary epithelial cells (IHMEC) as well as high levels of SEPT9 expression in the majority (61%) of the BCCs studied, unlike IHMECs. Expression profiling of variant SEPT9 transcripts and translated products revealed that high expression of the variant, SEPT9_v1, in contrast to other variants, was widespread in BCCs (55% of the BCCs) but not in IHMECs. High expression of SEPT9_v1 was also observed in primary breast cancer samples by immunohistochemical studies. We subsequently examined the phenotypic consequences of SEPT9_v1 expression in human breast cells. Retroviral expression of SEPT9_v1 in IHMEC cell culture models showed that SEPT9_v1 accelerated growth kinetics, stimulated cell motility, promoted invasion in Matrigel Transwell assays, increased genomic instability with the development of aneuploidy, and stimulated morphologic changes. Significant cytokinesis defects and disruption of tubulin microfilaments were also observed by immunofluorescence when SEPT9_v1 was ectopically expressed in IHMECs. Furthermore, SEPT9_v1 markedly enhanced neoplastic transformation in Hs578T cells, a BCC with no endogenous expression of the SEPT9_v1 isoform. Small interfering RNA-mediated and short hairpin RNA-mediated inhibition of SEPT9_v1 expression in two BCCs with high levels of endogenous SEPT9_v1 expression inhibited neoplastic growth properties of the cells. Taken together, our findings suggest that increased SEPT9_v1 expression contributes to the malignant pathogenesis of some breast tumors.

Original languageEnglish (US)
Pages (from-to)8554-8564
Number of pages11
JournalCancer Research
Volume67
Issue number18
DOIs
StatePublished - Sep 15 2007
Externally publishedYes

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Breast Neoplasms
Phenotype
Breast
Small Interfering RNA
Epithelial Cells
Septins
Cytokinesis
Genomic Instability
Aneuploidy
Tubulin
Growth
Actin Cytoskeleton
Cell Movement
Fluorescent Antibody Technique
Protein Isoforms
Carcinogenesis
Cell Culture Techniques
Genes
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gonzalez, M. E., Peterson, E. A., Privette, L. M., Loffreda-Wren, J. L., Kalikin, L. M., & Petty, E. M. (2007). High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. Cancer Research, 67(18), 8554-8564. https://doi.org/10.1158/0008-5472.CAN-07-1474

High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. / Gonzalez, Maria E.; Peterson, Esther A.; Privette, Lisa M.; Loffreda-Wren, Janice L.; Kalikin, Linda M.; Petty, Elizabeth M.

In: Cancer Research, Vol. 67, No. 18, 15.09.2007, p. 8554-8564.

Research output: Contribution to journalArticle

Gonzalez, ME, Peterson, EA, Privette, LM, Loffreda-Wren, JL, Kalikin, LM & Petty, EM 2007, 'High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes', Cancer Research, vol. 67, no. 18, pp. 8554-8564. https://doi.org/10.1158/0008-5472.CAN-07-1474
Gonzalez ME, Peterson EA, Privette LM, Loffreda-Wren JL, Kalikin LM, Petty EM. High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. Cancer Research. 2007 Sep 15;67(18):8554-8564. https://doi.org/10.1158/0008-5472.CAN-07-1474
Gonzalez, Maria E. ; Peterson, Esther A. ; Privette, Lisa M. ; Loffreda-Wren, Janice L. ; Kalikin, Linda M. ; Petty, Elizabeth M. / High SEPT9_v1 expression in human breast cancer cells is associated with oncogenic phenotypes. In: Cancer Research. 2007 ; Vol. 67, No. 18. pp. 8554-8564.
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