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. 2009 Jun;20(2):117-21.
doi: 10.3802/jgo.2009.20.2.117. Epub 2009 Jun 29.

Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers

Kyung-Do Ki  1 , Seo-Yun Tong, Chu-Yeop Huh, Jong-Min Lee, Seon-Kyung Lee, Sung-Gil Chi
Affiliations

Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers

Kyung-Do Ki et al. J Gynecol Oncol. 2009 Jun.

Abstract

Objective: To define the molecular basis of TGF-beta1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta1, TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling pathway, in human cervical cancers.

Methods: Expression of TGF-beta1, TGF-beta1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by quantitative genomic PCR.

Results: Abnormal overexpression of TGF-beta1 and abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis.

Conclusion: Our study demonstrates that disruption of TGF-beta/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor suppression function.

Keywords: Cervical cancer; Expression; TGF-β/Smads.

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Figures

Fig. 1
Fig. 1
TGF-β1, TGF-βRI and TGF-βRII expression (Quantitative reverse transcription-polymerase chain reaction analysis). N: normal cervix tissues, T: cervical tumor tissues
Fig. 2
Fig. 2
Smads expression (Quantitative reverse transcription-polymerase chain reaction analysis). N: normal cervix tissues, T: cervical tumor tissues
Fig. 3
Fig. 3
Mutational analysis of Tβ1R-II transcripts (reverse transcription-polymerase chain reaction-single-strand-conformation-polymorphism analysis).
Fig. 4
Fig. 4
Mutational analysis of Smad transcripts (reverse transcription-polymerase chain reaction-single-strand-conformation-polymorphism analysis). Abnormal migration shift of ssDNA (mutational sequence alteration, arrow). Smad2: 2 of 50 (4%) cervical cancers, Smad3: 0 of 50 (0%) cervical cancers, Smad4: 1 of 50 (2%) cervical cancers. N: normal cervix tissues, T: cervical tumor tissues
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