J Gynecol Oncol.  2009 Jun;20(2):117-121. 10.3802/jgo.2009.20.2.117.

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

• Ki KD
• Tong SY
• Huh CY
• Lee JM
• Lee SK
• Chi SG

• KMID: 2245095
• DOI: http://doi.org/10.3802/jgo.2009.20.2.117

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.

Keyword

TGF-beta/Smads; Cervical cancer; Expression

MeSH Terms

Humans
Polymerase Chain Reaction
RNA, Messenger
Transforming Growth Factor beta1
Uterine Cervical Neoplasms
RNA, Messenger
Transforming Growth Factor beta1

Figure

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  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

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  Fig. 2 Smads expression (Quantitative reverse transcription-polymerase chain reaction analysis). N: normal cervix tissues, T: cervical tumor tissues

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  Fig. 3 Mutational analysis of Tβ1R-II transcripts (reverse transcription-polymerase chain reaction-single-strand-conformation-polymorphism analysis).

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  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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