Promoter region methylation and loss of protein expression of PTEN and significance in cervical cancer

Abstract

Abstract. The genetic basis underlying cervical tumorigenesis and progression are largely unknown. Phosphatase and tensin homologue (PTEN) is a tumor suppressor gene, and genetic changes of PTEN occurs in various types of cancer suggesting that the inactivation of PTEN may play an important role in the pathogenesis of a variety of human malignancies. In the present study, 102 cervical cancer specimens were examined for the expression of the PTEN gene and promoter methylation using methylation-specific-polymerase chain reaction and immunohistochemistry. The PTEN gene mutation was also assessed using PCR single-strand conformational polymorphism. We examined the correlation between PTEN expression and its associated methylation status and the clinical characteristics of cervical cancer. The results showed that there was one case of an A to G point mutation on exon 9 of the PTEN gene in the cervical cancer tissues. This mutation caused the change of aspartic acid to glycine, and the rate of mutation was 1%. The PTEN gene methylation rate of cervical cancer was 62% (63/102) and the rate was associated with the International Federation of Gynecology and Obstetrics stage, cell differentiation, tumor size and lymph node metastasis (P<0.05). The positive rate of PTEN expression was 49% (50/102) in cervical carcinoma and the PTEN expression between stage I-II and III-IV [60 (27/45) vs. 40% (23/57)] was statistically significant (P<0.01). The PTEN gene expression between the metastasis and no lymph node metastasis groups [26 (10/38) vs. 63% (40/64)] was significantly different (P<0.01). The PTEN gene promoter methylation and its protein expression had a significant correlation (P= 0.042). These results suggest that hypermethylation can inactivate the transcription of PTEN and reduce its protein expression. Downregulated PTEN expression is involved in the pathogenesis, invasion and metastasis of cervical cancer, possibly by regulating the balance between apoptosis and proliferation. Therefore, the PTEN expression may be a good marker for the prognosis of cervical cancer.

The Relationship between the Methylation of Promoter Regions of Tumor Suppressor Genes PTEN and APC with Endometrial Cancer

“…In our estimate, the prevalence of PTEN methylation was 11.54% and 28.57% in patients' blood and tumor tissues, respectively. QI et al, (2014) showed that the frequency of PTEN promoter hypermethylation was 62% in tumor tissues of patients with cervical cancer where the methylation of the PTEN promoter was significantly related to the tumor grade, metastasis, and tumor stage (P<0.05). They found a significant association between the promoter methylation of PTEN and cervical cancer (P=0.042).…”

miR-21 inhibitor suppresses cell proliferation and colony formation through regulating the PTEN/AKT pathway and improves paclitaxel sensitivity in cervical cancer cells

“…Numerous heterozygotes are deleted in cervical cancer tissues, which are located in D10S198 and D10S192 sites (31). It has been suggested that inactivation of the PTEN gene and inhibition of protein expression may promote the progression of cervical cancer (32,33). However, the PI3K/AKT signaling pathway is abnormally activated in cervical cancer tissues (34).…”

Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

“…In cervical cancer, PTEN variants were shown to be associated with HPV-negative adenocarcinoma [75], although it was not reproduced in other studies [76]. The epigenetic regulation of gene expression seems to be relevant for PTEN as it is hypermethylated in cervical cancer and associated with the disease stage [77] and histological type [78], which is consistent with lower levels of PTEN and PTEN silencing [76,79]. The methylation events were also reported to be affected by the SNV in the CpG islands c.-9C > G, which modifies the methylation status and thus gene expression [80].…”