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Article

PTEN mutation, methylation and expression in breast cancer patients

  • Authors:
    • Hong‑Yan Zhang
    • Feng Liang
    • Zhi‑Ling Jia
    • San‑Tai Song
    • Ze‑Fei Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, General Hospital of Beijing Military Area, Beijing 100700, P.R. China, Department of General Surgery, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China, Department of Breast Cancer, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, P.R. China
  • Pages: 161-168
    |
    Published online on: May 8, 2013
       https://doi.org/10.3892/ol.2013.1331
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Abstract

The tumor suppressor gene, PTEN, has previously been demonstrated to be involved in breast tumorigenesis and tumor progression. The aim of the present study was to investigate the expression and significance of PTEN in breast carcinomas, to detect the mutation frequency of PTEN in sporadic breast carcinoma tissues and to determine the association between PTEN promoter methylation and gene expression. Immunohistochemical methods were used to analyze the expression of the PTEN gene in 146 cases of breast carcinoma and 10 cases of normal breast tissue closely adjacent to the carcinoma. Polymerase chain reaction‑single strand conformation polymorphism (PCR‑SSCP) analysis was used to analyze conformation polymorphisms in 45 breast carcinoma and 10 normal breast tissues. Point mutations of abnormal single stranded conformation were detected by DNA sequencing. The methylation of the PTEN promoter was analyzed by methylation‑specific PCR. Expression of PTEN was detected in 57.5% (84/146) of patients with breast carcinoma. By contrast, PTEN expression was detected in 100% of normal samples. Expression of PTEN was found to negatively correlate with the tumor size, the pathological stage and the expression of the estrogen receptor (ER) and the progesterone receptor (PR) in breast cancer. The 2‑year disease‑free survival of patients with a high expression of PTEN was higher compared with those with low PTEN expression (P<0.05). Missense mutations in exon 2 of PTEN were identified in 1/45 breast cancer cases. PTEN promoter methylation was detected in 31.1% (14/45) of breast carcinomas, of which 64.3% (9/14) were associated with a loss of PTEN expression. The tumor suppressor gene, PTEN, was abnormally expressed in the breast carcinomas. The number of PTEN mutations were low (1/45) in the sporadic breast cancer cases analyzed in the present study and PTEN promoter methylation may have been the main mechanism leading to the decreased expression of PTEN. These results indicate that PTEN is important for the tumorigenesis, development and prognosis of breast cancer.
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1. 

Tamura M, Gu J, Matsumoto K, Aota S, Parsons R and Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 280:1614–1617. 1998. View Article : Google Scholar : PubMed/NCBI

2. 

Waite KA and Eng C: Protean PTEN: form and function. Am J Hum Genet. 70:829–844. 2002. View Article : Google Scholar : PubMed/NCBI

3. 

Lu Y, Lin YZ, LaPushin R, Cuevas B, Fang X, Yu SX, Davies MA, Khan H, Furui T, Mao M, Zinner R, Hung MC, Steck P, Siminovitch K and Mills GB: The PTEN/MMAC1/TEP tumor suppressor gene decreases cell growth and induces apoptosis and anoikis in breast cancer cells. Oncogene. 18:7034–7045. 1999. View Article : Google Scholar : PubMed/NCBI

4. 

Weng LP, Brown JL and Eng C: PTEN coordinates (G1) arrest by down-regulating cyclin D1 via its protein phosphatase activity and up-regulating p27 via its lipid phosphatase activity in a breast cancer model. Hum Mol Genet. 10:599–604. 2001. View Article : Google Scholar : PubMed/NCBI

5. 

Tamguney T and Stokoe D: New insights into PTEN. J Cell Sci. 120:4071–4079. 2007. View Article : Google Scholar : PubMed/NCBI

6. 

Marsh DJ, Coulon V, Lunetta KL, Rocca-Serra P, Dahia PL, Zheng Z, Liaw D, Caron S, Duboué B, Lin AY, Richardson AL, Bonnetblanc JM, Bressieux JM, Cabarrot-Moreau A, Chompret A, Demange L, Eeles RA, Yahanda AM, Fearon ER, Fricker JP, Gorlin RJ, Hodgson SV, Huson S, Lacombe D, Eng C, et al: Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation. Hum Mol Genet. 7:507–515. 1998. View Article : Google Scholar : PubMed/NCBI

7. 

Baeza N, Weller M, Yonekawa Y, Kleihues P and Ohgaki H: PTEN methylation and expression in glioblastomas. Acta Neuropathol. 106:479–485. 2003. View Article : Google Scholar : PubMed/NCBI

8. 

Freihoff D, Kempe A, Beste B, Wappenschmidt B, Kreyer E, Hayashi Y, Meindl A, Krebs D, Wiestler OD, von Deimling A and Schmutzler RK: Exclusion of a major role for the PTEN tumour-suppressor gene in breast carcinomas. Br J Cancer. 79:754–758. 1999. View Article : Google Scholar : PubMed/NCBI

9. 

Bose S, Wang SI, Terry MB, Hibshoosh H and Parsons R: Allelic loss of chromosome 10q23 is associated with tumor progression in breast carcinomas. Oncogene. 17:123–127. 1998. View Article : Google Scholar : PubMed/NCBI

10. 

Garcia JM, Silva JM, Dominguez G, Gonzalez R, Navarro A, Carretero L, Provencio M, España P and Bonilla F: Allelic loss of the PTEN region (10q23) in breast carcinomas of poor pathophenotype. Breast Cancer Res Treat. 57:237–243. 1999. View Article : Google Scholar : PubMed/NCBI

11. 

Perren A, Weng LP, Boag AH, Ziebold U, Thakore K, Dahia PL, Komminoth P, Lees JA, Mulligan LM, Mutter GL and Eng C: Immunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast. Am J Pathol. 155:1253–1260. 1999. View Article : Google Scholar : PubMed/NCBI

12. 

Bose S, Crane A, Hibshoosh H, Mansukhani M, Sandweis L and Parsons R: Reduced expression of PTEN correlates with breast cancer progression. Hum Pathol. 33:405–409. 2002. View Article : Google Scholar : PubMed/NCBI

13. 

Depowski PL, Rosenthal SI and Ross JS: Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol. 14:672–676. 2001. View Article : Google Scholar : PubMed/NCBI

14. 

Lee JS, Kim HS, Kim YB, Lee MC, Park CS and Min KW: Reduced PTEN expression is associated with poor outcome and angiogenesis in invasive ductal carcinoma of the breast. Appl Immunohistochem Mol Morphol. 12:205–210. 2004. View Article : Google Scholar : PubMed/NCBI

15. 

Shoman N, Klassen S, McFadden A, Bickis MG, Torlakovic E and Chibbar R: Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Mod Pathol. 18:250–259. 2005. View Article : Google Scholar : PubMed/NCBI

16. 

Campbell RA, Bhat-Nakshatri P, Patel NM, Constantinidou D, Ali S and Nakshatri H: Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance. J Biol Chem. 276:9817–9824. 2001. View Article : Google Scholar : PubMed/NCBI

17. 

Keshet I, Lieman-Hurwitz J and Cedar H: DNA methylation affects the formation of active chromatin. Cell. 44:535–543. 1986. View Article : Google Scholar : PubMed/NCBI

18. 

Antequera F: Structure, function and evolution of CpG island promoters. Cell Mol Life Sci. 60:1647–1658. 2003. View Article : Google Scholar : PubMed/NCBI

19. 

Soria JC, Lee HY, Lee JI, Wang L, Issa JP, Kemp BL, Liu DD, Kurie JM, Mao L and Khuri FR: Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation. Clin Cancer Res. 8:1178–1184. 2002.PubMed/NCBI

20. 

Khan S, Kumagai T, Vora J, Bose N, Sehgal I, Koeffler PH and Bose S: PTEN promoter is methylated in a proportion of invasive breast cancers. Int J Cancer. 112:407–410. 2004. View Article : Google Scholar : PubMed/NCBI

21. 

Shaw RJ and Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 441:424–430. 2006. View Article : Google Scholar : PubMed/NCBI

22. 

Janzen V and Scadden DT: Stem cells: good, bad and reformable. Nature. 441:418–419. 2006. View Article : Google Scholar : PubMed/NCBI

23. 

Simpson L and Parsons R: PTEN: life as a tumor suppressor. Exp Cell Res. 264:29–41. 2001. View Article : Google Scholar : PubMed/NCBI

24. 

Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR and Greenberg ME: Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 275:661–665. 1997. View Article : Google Scholar : PubMed/NCBI

25. 

Ramaswamy S, Nakamura N, Vazquez F, Batt DB, Perera S, Roberts TM and Sellers WR: Regulation of G1 progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway. Proc Natl Acad Sci USA. 96:2110–2115. 1999. View Article : Google Scholar : PubMed/NCBI

26. 

Stahl JM, Sharma A, Cheung M, Zimmerman M, Cheng JQ, Bosenberg MW, Kester M, Sandirasegarane L and Robertson GP: Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 64:7002–7010. 2004. View Article : Google Scholar : PubMed/NCBI

27. 

Curtin JA, Fridlyand J, Kageshita T, Patel HN, Busam KJ, Kutzner H, Cho KH, Aiba S, Bröcker EB, LeBoit PE, Pinkel D and Bastian BC: Distinct sets of genetic alterations in melanoma. N Engl J Med. 353:2135–2147. 2005. View Article : Google Scholar : PubMed/NCBI

28. 

Lian Z and Di Cristofano A: Class reunion: PTEN joins the nuclear crew. Oncogene. 24:7394–7400. 2005. View Article : Google Scholar : PubMed/NCBI

29. 

Miller TW, Pérez-Torres M, Narasanna A, Guix M, Stål O, Pérez-Tenorio G, Gonzalez-Angulo AM, Hennessy BT, Mills GB, Kennedy JP, Lindsley CW and Arteaga CL: Loss of phosphatase and tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer. Cancer Res. 69:4192–4201. 2009. View Article : Google Scholar

30. 

Saal LH, Johansson P, Holm K, Gruvberger-Saal SK, She QB, Maurer M, Koujak S, Ferrando AA, Malmström P, Memeo L, Isola J, Bendahl PO, Rosen N, Hibshoosh H, Ringnér M, Borg A and Parsons R: Poor prognosis in carcinoma is associated with a gene expression signature of aberrant PTEN tumor suppressor pathway activity. Proc Natl Acad Sci USA. 104:7564–7569. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zhang HY, Liang F, Jia ZL, Song ST and Jiang ZF: PTEN mutation, methylation and expression in breast cancer patients. Oncol Lett 6: 161-168, 2013.
APA
Zhang, H., Liang, F., Jia, Z., Song, S., & Jiang, Z. (2013). PTEN mutation, methylation and expression in breast cancer patients. Oncology Letters, 6, 161-168. https://doi.org/10.3892/ol.2013.1331
MLA
Zhang, H., Liang, F., Jia, Z., Song, S., Jiang, Z."PTEN mutation, methylation and expression in breast cancer patients". Oncology Letters 6.1 (2013): 161-168.
Chicago
Zhang, H., Liang, F., Jia, Z., Song, S., Jiang, Z."PTEN mutation, methylation and expression in breast cancer patients". Oncology Letters 6, no. 1 (2013): 161-168. https://doi.org/10.3892/ol.2013.1331
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang HY, Liang F, Jia ZL, Song ST and Jiang ZF: PTEN mutation, methylation and expression in breast cancer patients. Oncol Lett 6: 161-168, 2013.
APA
Zhang, H., Liang, F., Jia, Z., Song, S., & Jiang, Z. (2013). PTEN mutation, methylation and expression in breast cancer patients. Oncology Letters, 6, 161-168. https://doi.org/10.3892/ol.2013.1331
MLA
Zhang, H., Liang, F., Jia, Z., Song, S., Jiang, Z."PTEN mutation, methylation and expression in breast cancer patients". Oncology Letters 6.1 (2013): 161-168.
Chicago
Zhang, H., Liang, F., Jia, Z., Song, S., Jiang, Z."PTEN mutation, methylation and expression in breast cancer patients". Oncology Letters 6, no. 1 (2013): 161-168. https://doi.org/10.3892/ol.2013.1331
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