Overexpression of the TGF-β antagonist Smad7 in endometrial cancer

Sean Christopher Dowdy, Andrea Mariani, Monica M. Reinholz, Gary Keeney, Thomas C. Spelsberg, Karl C. Podratz, Ralf Janknecht

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

We have shown that her2/neu may activate the Smad7 promoter in endometrial, ovarian, and breast cancer cell lines. Elevated Smad7 levels could then antagonize the TGF-β pathway, leading to a reduction in tumor surveillance and potential cancer formation. Our aim was to determine if Smad7 was in fact overexpressed in endometrial cancers and whether Smad7 RNA levels correlated with tumor grade or clinical endpoints. Snap-frozen endometrial cancer specimens from 16 patients with grade 1 disease and 23 patients with grade 3 disease were obtained. Additionally, the endometrium from 18 patients who underwent hysterectomy for benign indications was collected as a control. RNA was extracted and subjected to quantitative real-time PCR to determine the degree of Smad7 RNA expression. Clinical outcomes including time to recurrence were recorded through retrospective chart review. Smad7 transcripts in the tumors were over 11-fold elevated on average than in controls (P < 0.001). There was no significant difference in Smad7 RNA between grades 1 and 3 tumors. For the 19 patients who recurred, median time to recurrence was 56.3 months for those with low Smad7 expression versus 30 months for those with high Smad7 expression (P < 0.004). Smad7 appears to be upregulated in endometrial cancers compared to normal endometrium. Furthermore, high Smad7 gene expression was associated with a shorter time to recurrence. Given that many endometrial cancers have been shown to be TGF-β-unresponsive, Smad7 should be investigated as a potential target to restore TGF-β responsiveness and limit tumor growth.

Original languageEnglish (US)
Pages (from-to)368-373
Number of pages6
JournalGynecologic Oncology
Volume96
Issue number2
DOIs
StatePublished - Feb 2005

Fingerprint

Endometrial Neoplasms
RNA
Neoplasms
Endometrium
Recurrence
Hysterectomy
Ovarian Neoplasms
Real-Time Polymerase Chain Reaction
Breast Neoplasms
Gene Expression
Cell Line
Growth

Keywords

  • Endometrial cancer
  • HER2/Neu
  • Ras
  • Smad7
  • TGF-β

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Dowdy, S. C., Mariani, A., Reinholz, M. M., Keeney, G., Spelsberg, T. C., Podratz, K. C., & Janknecht, R. (2005). Overexpression of the TGF-β antagonist Smad7 in endometrial cancer. Gynecologic Oncology, 96(2), 368-373. https://doi.org/10.1016/j.ygyno.2004.10.006

Overexpression of the TGF-β antagonist Smad7 in endometrial cancer. / Dowdy, Sean Christopher; Mariani, Andrea; Reinholz, Monica M.; Keeney, Gary; Spelsberg, Thomas C.; Podratz, Karl C.; Janknecht, Ralf.

In: Gynecologic Oncology, Vol. 96, No. 2, 02.2005, p. 368-373.

Research output: Contribution to journalArticle

Dowdy, SC, Mariani, A, Reinholz, MM, Keeney, G, Spelsberg, TC, Podratz, KC & Janknecht, R 2005, 'Overexpression of the TGF-β antagonist Smad7 in endometrial cancer', Gynecologic Oncology, vol. 96, no. 2, pp. 368-373. https://doi.org/10.1016/j.ygyno.2004.10.006
Dowdy, Sean Christopher ; Mariani, Andrea ; Reinholz, Monica M. ; Keeney, Gary ; Spelsberg, Thomas C. ; Podratz, Karl C. ; Janknecht, Ralf. / Overexpression of the TGF-β antagonist Smad7 in endometrial cancer. In: Gynecologic Oncology. 2005 ; Vol. 96, No. 2. pp. 368-373.
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