PTEN and p53 abnormalities are indicative and predictive factors for endometrial carcinoma

Inaba, Fujiyuki; Kawamata, Hitoshi; Teramoto, Tadahisa; Fukasawa, Ichio; Inaba, Noriyuki; Fujimori, Takahiro

doi:10.3892/or.13.1.17

Cited by 16 publications

(20 citation statements)

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“…p53 activates PTEN gene expression, which explains a decreased PTEN expression in p53-null MEFs as seen by Wang et al (22) and in 293 cells by Chappell et al (23) under stress induced by serum deprivation. However, it is difficult to understand why in vivo when p53 is significantly increased we do not see the corresponding PTEN protein increase, which would be expected based on the transcriptional regulation of PTEN of p53 (6,24,25). One possible explanation is that the increased p53 protein noted on immunohistochemistry reflects increased p53 stability (hence increased immunostaining) in the context of TP53 mutations.…”

Section: Discussionmentioning

confidence: 69%

“…Interestingly, PTEN deficiency observed by immunohistochemical staining in patient cells was found to be associated with elevated p53 protein levels in the early phase of carcinogenesis (6)(7)(8). We have recently reported that PTEN protein is easily degraded in lymphoblast cells from Cowden syndrome patients possessing PTEN promoter mutations in the context of elevated p53 levels (9).…”

Section: Introductionmentioning

confidence: 99%

“…Yet, it is difficult to understand why significant increases of p53 protein level correlate with no or reduced expression of PTEN protein in variety of cancers, particularly considering that p53 is known to up-regulate PTEN expression (6,7). By using both normal human lymphoblast cells and MCF7 breast cancer cells, we now show that p53 is able to down-regulate PTEN partially by activating caspases under stress induced by proteasome inhibition.…”

Section: Introductionmentioning

confidence: 99%

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p53 Down-Regulates Phosphatase and Tensin Homologue Deleted on Chromosome 10 Protein Stability Partially through Caspase-Mediated Degradation in Cells with Proteasome Dysfunction

Tang

Eng

2006

Cancer Research

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There has been intense investigation regarding the interaction between the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and p53 tumor suppressors. p53 has been shown to up-regulate PTEN expression as a transcriptional activator. However, clinical observations by immunohistochemistry studies indicate that significant increases in p53 protein levels coexist with reduced or absent expression of PTEN protein in a variety of neoplasias. In this study, we propose a mechanism that begins to explain how p53 can both up-regulate and down-regulate PTEN. We have found that PTEN protein is down-regulated under proteasome dysfunction induced by proteasome inhibitor MG132 in both human lymphoblast cells and MCF7 cells. The reduction of PTEN is coincident with elevated p53 protein levels and the association between PTEN and p53 but independent of its phosphatase activities. Quantitative reverse transcription-PCR indicates that proteasome inhibition does not reduce PTEN message levels but affects PTEN protein stability. The p53 inhibitor, pifithrin-A, is able to attenuate the effect of proteasome inhibition. Using ectopic expression studies in p53-null mouse embryonic fibroblasts and p53/PTEN-null PC3 cells, we show that PTEN is more stable in p53-null cells compared with p53-expressing cells. Inhibition of caspases, the downstream targets of p53, particularly caspase-3, can partially restore the stability of PTEN. This study provides the first evidence that p53 is able to down-regulate PTEN protein stability in stressed cells. Our study sheds some light on the mechanisms that regulate PTEN protein stability, which is important to fully elucidate to comprehend the broad neoplastic manifestations of Cowden syndrome/Bannayan-Riley-Ruvalcaba and sporadic cancers.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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p53 Down-Regulates Phosphatase and Tensin Homologue Deleted on Chromosome 10 Protein Stability Partially through Caspase-Mediated Degradation in Cells with Proteasome Dysfunction

Tang

Eng

2006

Cancer Research

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“…PTEN is a close second to p53 in terms of its mutation frequency and probably rivals p53 in its ability to regulate multiple signal transduction pathways that affect diverse and vital cellular functions [1,3,11,12] . PTEN tumor suppressor gene mutations are the most frequent genetic lesions in endometrial adenocancinomas of the endometrioid subtype.…”

Section: Discussionmentioning

confidence: 99%

Correlation between PTEN expression and PI3K/Akt signal pathway in endometrial carcinoma

Gao

Xia

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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In order to investigate the role of the PTEN expression in carcinogenesis and development of endometrial carcinoma and clarify whether and how PTEN and PI3K/Akt pathway relate to endometrial carcinoma, the expression of PTEN and phospho-Akt was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods and Western-blot from 24 cases of endometrial carcinoma, 10 cases of endometrial atypical hyperplasia, 10 cases of endometrial hyperplasia, and 10 cases of normal endometrium. SP immunohistochemical methods were used to measure levels of PTEN protein expression in following 5 study groups: 31 cases of endometrium in proliferative phase, 30 cases of endometrium in secretory phase, 71 cases of endometrial hyperplasia, 25 cases of atypical hyperplasia and 73 cases of endometrial carcinoma. Immunostaining score of PTEN was 3.39+/-0.15 in proliferative phase, 1.90+/-0.21 in secretory phase, 3.34+/-0.29 in endometrial hyperplasia, 0.62+/-0.11 in atypical hyperplasia, and 0.74+/-0.19 in endometrial carcinoma, respectively. PTEN mRNA relative value in normal endometrium, endometrial hyperplasia, endometrial atypical hyperplasia, and endometrial carcinoma was 2.45+/-0.51, 2.32+/-0.32, 0.46+/-0.11, and 0.35+/-0.13 respectively. The expression levels of PTEN mRNA and protein in patients with endometrial carcinoma and atypical hyperplasia were significantly lower than in those of proliferative phase and with endometrial hyperplasia. The level of PTEN expression in patients with endometrial carcinoma was significantly related to tissue type (P<0.005), differentiation (P<0.05) and clinical stage (P<0.05), but not to depth of myometrium invasion (P>0.05). Western blot analysis revealed that Phospho-Akt level in PTEN negative cases was significantly higher, and there was a negative correlation between PTEN and phospho-Akt (r=-0.8973, P<0.0001). It was suggested that loss of PTEN expression was an early event in endometrial tumorigenesis. The phosphorylation of Akt induced by the loss of PTEN took part in the tumorigenesis and development of endometrial carcinoma.

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“…In the subgroup analysis, they observed that PTEN expression was seen in 41.4% in endometrioid and 22.7% in nonendometrioid groups; the differences between the groups were nonsignificant. Inaba et al16 detected PTEN expression in 55 (60%) of 92 women with EC. Daniilidou et al 17 detected PTEN expression in 35 (71.4%) of 49 patients with endometrioid type EC.…”

mentioning

confidence: 99%

Expression of PTEN and β-Catenin and Their Relationship With Clinicopathological and Prognostic Factors in Endometrioid Type Endometrial Cancer

Sal

Demirkıran

Erenel³

et al. 2016

International Journal of Gynecological Cancer

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PTEN and β-catenin expressions cannot be used to determine prognosis in patients with EC as PTEN and β-catenin staining status were found to have no significant effect on 5-year overall survival and disease-free survival. Positive staining of PTEN may be associated with increased myometrial invasion. Meta-analyses and broader studies are needed to evaluate the prognostic value of PTEN and β-catenin in EC.

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PTEN and p53 abnormalities are indicative and predictive factors for endometrial carcinoma

Cited by 16 publications

References 0 publications

p53 Down-Regulates Phosphatase and Tensin Homologue Deleted on Chromosome 10 Protein Stability Partially through Caspase-Mediated Degradation in Cells with Proteasome Dysfunction

p53 Down-Regulates Phosphatase and Tensin Homologue Deleted on Chromosome 10 Protein Stability Partially through Caspase-Mediated Degradation in Cells with Proteasome Dysfunction

Correlation between PTEN expression and PI3K/Akt signal pathway in endometrial carcinoma

Expression of PTEN and β-Catenin and Their Relationship With Clinicopathological and Prognostic Factors in Endometrioid Type Endometrial Cancer

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