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

Objective: To define the molecular basis of TGF-beta 1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta 1, TGF-beta 1 receptors, and Smads, the regulators of the TGF-beta 1 signaling pathway, in human cervical cancers. Methods: Expression of TGF-beta 1, TGF-beta 1 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-beta 1, TGF-beta 1 receptors and Smads was also measured by quantitative genomic PCR. Results: Abnormal overexpression of TGF-beta 1 and abnormal reduction of type II TGF-beta 1 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-beta 1 1's tumor suppression function.