• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of amjpatholAmerican Journal of Pathology For AuthorsAmerican Journal of Pathology SubscribeAmerican Journal of Pathology SearchAmerican Journal of Pathology Current IssueAmerican Journal of Pathology About the JournalAmerican Journal of Pathology
Am J Pathol. Jun 2001; 158(6): 1895–1898.
PMCID: PMC1891981

PTEN, a Protean Tumor Suppressor

The molecular biology of the PTEN tumor suppressor gene is as multifaceted as the range of sporadic human malignancies in which it has been implicated. Multiple mechanisms can inactivate PTEN in glioblastoma, melanoma, and carcinomas of the thyroid, breast, prostate, endometrium, and ovary. Initial impressions, based on mutational analysis alone, that ovarian cancer PTEN inactivation is infrequent bear revision in light of a 27% frequency of lost PTEN protein expression reported by Kurose and colleagues in this issue of The American Journal of Pathology. 1 Only 8% of PTEN protein nonexpressing ovarian adenocarcinomas are explained by combined allelic imbalance (loss of heterozygosity) and mutation, suggesting that transcriptional silencing by epigenetic mechanisms may be yet an additional means of modifying PTEN activity. Although they show for ovarian carcinoma that PTEN function can be delimited by an identifiable and consistent repertoire of downstream effectors, such as the Akt pathway, the consequences of PTEN inactivation are nonuniform in different tissues. Thus, in the endometrium PTEN acts as a gatekeeper for initiation of carcinogenesis, yet in prostate cancer and melanoma it defines a much later event, metastasis. Tissue context determines the molecular events that inactivate PTEN and heavily modify the resultant phenotype.

A Multitude of Inactivating Mechanisms

Functional inactivation of the PTEN gene may occur through deletional and mutational mechanisms, and these are variably invoked between tumor types (Table 1) [triangle] and hereditary/sporadic settings. Thus, it is necessary to have an integrated and comprehensive snapshot of different modalities of PTEN inactivation before an accurate model of changing PTEN function can be concluded for a specific tumor type. Patients with Cowden syndrome have a high incidence of breast cancer caused by heritable constitutive structural mutations of the PTEN gene, 2-4 yet such mutations are rarely seen in sporadic breast cancer. Rather, the PTEN lesions of sporadic breast cancers are a deletion-induced hemizygous state. 5-7 Deletion of the PTEN region at 10q23 are also predominant findings in PTEN-deficient melanomas 8,9 and glioblastomas. 10-15 In contrast, both PTEN deletion and mutation are frequent events in sporadic endometrioid endometrial adenocarcinoma. 16-21 It should be remembered that technical variation can confound reproducibility of loss of heterozygosity and mutational data between laboratories. Deletion and mutation detection is affected by the extent to which normal tissue contaminates isolated lesional DNA, a process that varies between investigators. For example, denaturing gradient gel electrophoresis (DGGE) is particularly suited for detecting as low as 1 to 10% mutant DNA contribution. These problems are not unique to PTEN, but are compounded when multiple mechanisms must be evaluated in a single tumor type. Many of the literature inconsistencies between reported involvement of the PTEN gene in specific tumor types can be attributed to the methodologies used. Ovarian carcinoma is an example where the impression of the extent of altered PTEN genotype has been highly dependent on whether mutation alone, 22 or deletion and mutation 1,23 are evaluated.

Table 1.
PTEN Lesions (Deletion and/or Mutation) in Sporadic Human Malignancies

The mechanism of PTEN inactivation seems to be conserved in a given histological subtype of adenocarcinoma irrespective of the primary site. For example, PTEN inactivation in endometrioid adenocarcinomas of the ovary 1,24 and endometrium 18,21 have similar patterns of deletion and mutation. In contrast, PTEN mutation is quite rare in carcinomas with papillary serous differentiation irrespective of whether they occur in the ovary or endometrium. We can thus identify the histological mix 24 of tumors as another variable that must be considered in comparing results from series of cases derived from a common site.

Loss of PTEN function in endometrial, 21 breast, 7 prostate, 25 ovarian, 1 and melanocytic 9 tumors is more frequent than can be adequately explained by structural genomic changes alone. Careful exclusion of deletional and mutational mechanisms in these cases has led to the prediction of epigenetic mechanisms as yet another means by which this tumor suppressor can be silenced. Proving an epigenetic mechanism of PTEN silencing is technically nontrivial because of the large size (>250 kb) of its upstream regulatory region, the existence of a highly conserved processed pseudogene 26 with homology maintained up to 1 kb upstream of the translational start site, and technical challenges in linking epigenetic events with expression level. Recent reports of PTEN promoter methylation 27 in endometrial cancer, and reacquisition of PTEN expression on treatment of prostate cancer cells with the demethylating agent 5-azadeoxycytidine 25 are consistent with epigenetic mechanisms at work in these models.

Implication in Diverse Regulatory Pathways

In vitro cell line data has suggested that the tumor suppressor functions of PTEN, including G1 arrest and enabling of apoptosis, are mediated by a cascade that maintains the putative downstream factor Akt in a dephosphorylated state. 28,29 Thus, the prediction that PTEN protein and phospho-Akt have an inverse quantitative relationship. The article by Kurose and colleagues 1 (page xx, this issue) uses a series of primary sporadic ovarian cancers to confirm this inverse relationship between PTEN protein and phospho-Akt. This is an important extrapolation from a cell culture model, which is necessarily limited in representing the range of genetic variation and heterogeneity present in sporadic human tumors. Because the majority of ovarian cancers with elevated phospho-Akt levels are accompanied by demonstrable changes in PTEN function, PTEN presents itself as a major determinant of Akt-mediated apoptosis and G1 arrest in ovarian cancer. Mitotic arrest and cell death are, however, basic cellular functions controlled by a complex web of regulatory pathways that probably include elements outside the PTEN-Akt axis. The finding that p27 and cyclin D1 do not necessarily behave according to a simple linear model aligned with PTEN and Akt 1 suggests that these downstream events are indirect or subject to modification.

Additional functions of PTEN outside the Akt pathway have been proposed, and are still under active experimental consideration. These include control of cell adhesion and migration by dephosphorylation of focal adhesion kinases. 30,31 Although this might explain some of the altered functions expected in neoplastic transformation, the effect of PTEN on adhesion is probably a complex one that likely involves other intermediary molecules. 32

Nongenetic Modifiers

There must be as yet unidentified factors that are capable of significantly modifying the phenotypic presentation of cells with altered PTEN function. The constellation of sporadic human tumors characterized by PTEN inactivation (Table 1) [triangle] only partly overlaps with that of the heritable cancer syndrome caused by constitutive PTEN inactivation, Cowden syndrome. Cowden syndrome is often accompanied by thyroid (mainly follicular histology), breast, and endometrial cancers and benign hamartomatous lesions of the skin and brain. 33 Surprisingly, they have not been reported to have heightened incidences of ovarian and prostate adenocarcinomas or glioblastoma, sporadic tumor types that often have PTEN inactivation. One possible explanation is that existing series of Cowden syndrome patients are too small to precisely measure even significant changes in incidences of these tumors beyond their already low sporadic occurrence rates. There is also divergence of tumor spectrum between murine pten-deficient mice and human neoplasia. pten knockout mice develop papillary thyroid, breast, prostate, and endometrial tumors, but not glioblastomas or ovarian carcinoma. 34,35 One constitutively pten-deficient mouse model 36 resulted in lymphoproliferative lesions that are not seen in human Cowden syndrome and have not been otherwise associated with prominent somatic PTEN mutation. It is reasonable to postulate that a germ-line PTEN mutation such as knock-out murine models or Cowden patients may result in permanent compensatory changes during early development that in turn results in a different spectrum of tumors compared to sporadic somatic mutations. Thus, although heritable PTEN-deficient mice and Cowden patients have been useful in defining the tumor suppressor activity of PTEN, caution must be used in extrapolation between species, and to a sporadic setting.

Hormonal environment is one systemic factor that may modulate physiological demand for PTEN protein, thereby defining a shifting normal baseline against which the functional implications of PTEN loss must be measured. Normal PTEN expression increases in endometrial glands during the estrogenic follicular phase of the menstrual cycle, 37 and declines dramatically on introduction of the antiestrogenic hormone progesterone. It is unknown whether estrogen-associated increases in endometrial PTEN expression is part of a general mitogenic response, or whether there is a direct upstream link between the estrogen response pathway and the PTEN gene. Whatever the case, it seems that a rapidly dividing estrogen-stimulated endometrial gland has a greater PTEN requirement than a quiescent progesterone-exposed nonmitotic gland, and it is reasonable to conclude that these settings would respond differently to loss of PTEN function. Consistent with this notion is the fact that the primary epidemiological risk factor for PTEN-deficient endometrial carcinomas (endometrioid histological subtype) is protracted estrogen exposure. 38 The possibility of hormonal regulation of PTEN protein in other tissue types is largely unexplored. There is, however, enticing preliminary data that suggests that PTEN may inhibit cell growth through the MAP kinase-dependent insulin response pathway in an in vitro breast cancer model. 39

Early and Late Effects: Tumor Initiation Versus Metastasis

It is remarkable that PTEN inactivation may affect quite different stages of tumor evolution, being highly consistent in multiple examples of tumors at one site. In the case of endometrioid endometrial adenocarcinoma, loss of PTEN expression is usually invoked quite early on, in the manner of a gene that performs a gatekeeper function. 40 PTEN mutation, deletion, and loss of expression are seen in the premalignant phases of endometrial carcinogenesis, and appear at highest frequency (83%) in those adenocarcinomas that are preceded by a histologically evident premalignant hyperplasia (EIN, endometrial intraepithelial neoplasia) 21 and have an indolent, nonaggressive clinical course. Loss of PTEN function may even precede acquisition of cytological atypia, a histopathological feature long thought to distinguish the threshold between benign and premalignant endometrial disease. 21 Clear cell and endometrioid ovarian adenocarcinomas may also share deletion of the PTEN locus 41,42 with premalignant (endometriosis) tissues. 42

In contrast, PTEN inactivation in melanoma, 8 prostate carcinoma, 43 and glioblastoma, 11,13 is a marker for an aggressive subset of tumors likely to metastasize. Although metastasis is considered to be a late event in tumor progression, PTEN inactivation in these cases probably occurs earlier in tumor evolution. Even for those prostatic carcinomas that have metastasized, PTEN deletions are already widely present at the primary site. 43 Aggressive glioblastomas with PTEN loss of function are primarily high grade throughout, and PTEN inactivation does not often occur in tumors that undergo a progressive increase in grade during their growth. 15 The full manifestation of a complex phenotype such as metastasis and acquisition of a contributing single mutation (such as PTEN) may be separated by a lag period, during which other mutations required for the full manifestation of this phenotype are accumulated. As a consequence, despite being an early event, PTEN mutations in some tumors may become important in later stages, such as metastasis and aggressive behavior.

Future Challenges

Compromise of PTEN function is widespread in human cancers, occurring in fully a third of some of the most common human malignancies. This has caught the keen attention of clinicians and scientists alike, and highlights the need to reconcile data garnered from a variety of settings. Enticing as it is to combine these in a sweeping model centered on a single gene, the truth is in the details. The basis of lost PTEN function is not yet completely explained, and investigation of whether epigenetic events are in fact a common mechanism of inactivation is a priority. Recent availability of antibody reagents applicable to paraffin-embedded tissues 7,21 will greatly facilitate continued use of primary human material in those experiments intended to relate PTEN gene expression to epigenetic modification. The effects of posttranslational factors on PTEN action have not yet been systematically studied. Cell-type-specific shifts in cellular compartmentalization of PTEN protein have been seen in conjunction with neoplastic transformation and cellular differentiation, 1,37,44 but the functional impact of these changes is unknown. Lastly, observed idiosyncrasies of tissue-specific PTEN inactivation mechanism and their resultant phenotype will be a useful tool for unraveling those factors that modify the functional requirements for PTEN protein, and the biological implications of their loss.


Address reprint requests to George L. Mutter, M.D., Department of Pathology, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115. E-mail: .ude.dravrah.hwb.scir@rettumg


1. Kurose K, Zhou X, Araki T, Cannistra S, Maher E, Eng C: Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am J Pathol 2001, 158:2097-2106 [PMC free article] [PubMed]
2. Liaw D, Marsh DJ, Li J, Dahia PL, Wang SI, Zheng Z, Bose S, Call KM, Tsou HC, Peacocke M, Eng C, Parsons R: Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. Nat Genet 1997, 16:64-67 [PubMed]
3. Nelen MR, van Staveren WC, Peeters EA, Hassel MB, Gorlin RJ, Hamm H, Lindboe CF, Fryns JP, Sijmons RH, Woods DG, Mariman EC, Padberg GW, Kremer H: Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. Hum Mol Genet 1997, 6:1383-1387 [PubMed]
4. Tsou HC, Teng DH, Ping XL, Brancolini V, Davis T, Hu R, Xie XX, Gruener AC, Schrager CA, Christiano AM, Eng C, Steck P, Ott J, Tavtigian SV, Peacocke M: The role of MMAC1 mutations in early-onset breast cancer: causative in association with Cowden syndrome and excluded in BRCA1-negative cases. Am J Hum Genet 1997, 61:1036-1043 [PMC free article] [PubMed]
5. Rhei E, Kang L, Bogomolniy F, Federici MG, Borgen PI, Boyd J: Mutation analysis of the putative tumor suppressor gene PTEN/MMAC1 in primary breast carcinomas. Cancer Res 1997, 57:3657-3659 [PubMed]
6. Teng D, Hu R, Lin H, Davis T, Iliev D, Frye C, Swedlund B, Hansen K, Vinson V, Gumpper K, Ellis L, El-Naggar A, Frazier M, Jassr S, Langford L, Lee J, Mills G, Pershouse M, Pollack R, Tornos C, Troncoso P, Yung W, Fujii G, Berson A, Bookstein R, Bolen J, Tavtigian S, Steck P: MMAC1/PTEN Mutations in primary tumor specimens and tumor cell lines. Cancer Res 1997, 57:5221-5225 [PubMed]
7. Perren A, Weng L, Boag A, Ziebold U, Thakore K, Dahia P, Lees J, Mulligan L, Mutter GL, Eng C: Immunocytochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breast. Am J Pathol 1999, 155:1253-1260 [PMC free article] [PubMed]
8. Celebi JT, Shendrik I, Silvers DN, Peacocke M: Identification of PTEN mutations in metastatic melanoma specimens. J Med Genet 2000, 37:653-657 [PMC free article] [PubMed]
9. Zhou XP, Gimm O, Hampel H, Niemann T, Walker MJ, Eng C: Epigenetic PTEN silencing in malignant melanomas without PTEN mutation. Am J Pathol 2000, 157:1123-1128 [PMC free article] [PubMed]
10. Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997, 275:1943-1947 [PubMed]
11. Rasheed BK, Stenzel TT, McLendon RE, Parsons R, Friedman AH, Friedman HS, Bigner DD, Bigner SH: PTEN gene mutations are seen in high-grade but not in low-grade gliomas. Cancer Res 1997, 57:4187-4190 [PubMed]
12. Wang SI, Puc J, Li J, Bruce JN, Cairns P, Sidransky D, Parsons R: Somatic mutations of PTEN in glioblastoma multiforme. Cancer Res 1997, 57:4183-4186 [PubMed]
13. Bostrom J, Cobbers JM, Wolter M, Tabatabai G, Weber RG, Lichter P, Collins VP, Reifenberger G: Mutation of the PTEN (MMAC1) tumor suppressor gene in a subset of glioblastomas but not in meningiomas with loss of chromosome arm 10q. Cancer Res 1998, 58:29-33 [PubMed]
14. Fults D, Pedone CA, Thompson GE, Uchiyama CM, Gumpper KL, Iliev D, Vinson VL, Tavtigian SV, Perry WL: Microsatellite deletion mapping on chromosome 10q and mutation analysis of MMAC1, FAS, and MXI1 in human glioblastoma multiforme. Int J Oncol 1998, 12:905-910 [PubMed]
15. Tohma Y, Gratas C, Biernat W, Peraud A, Fukuda M, Yonekawa Y, Kleihues P, Ohgaki H: PTEN (MMAC1) mutations are frequent in primary glioblastomas (de novo) but not in secondary glioblastomas. J Neuropathol Exp Neurol 1998, 57:684-689 [PubMed]
16. Risinger JI, Hayes AK, Berchuck A, Barrett JC: PTEN/MMAC1 mutations in endometrial cancers. Cancer Res 1997, 57:4736-4738 [PubMed]
17. Tashiro H, Blazes MS, Wu R, Cho KR, Bose S, Wang SI, Li J, Parsons R, Ellenson LH: Mutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignancies. Cancer Res 1997, 57:3935-3940 [PubMed]
18. Risinger JI, Hayes K, Maxwell GL, Carney ME, Dodge RK, Barrett JC, Berchuck A: PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics. Clin Cancer Res 1998, 4:3005-3010 [PubMed]
19. Simpkins SB, Peiffer-Schneider S, Mutch DG, Gersell D, Goodfellow PJ: PTEN mutations in endometrial cancers with 10q LOH: additional evidence for the involvement of multiple tumor suppressors. Gynecol Oncol 1998, 71:391-395 [PubMed]
20. Bussaglia E, del Rio E, Matias-Guiu X, Prat J: PTEN mutations in endometrial carcinomas: a molecular and clinicopathologic analysis of 38 cases. Hum Pathol 2000, 31:312-317 [PubMed]
21. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JPA, Lees J, Weng LP, Eng C: Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000, 92:924-930 [PubMed]
22. Maxwell GL, Risinger JI, Tong B, Shaw H, Barrett JC, Berchuck A, Futreal PA: Mutation of the PTEN tumor suppressor gene is not a feature of ovarian cancers. Gynecol Oncol 1998, 70:13-16 [PubMed]
23. Saito M, Okamoto A, Kohno T, Takakura S, Shinozaki H, Isonishi S, Yasuhara T, Yoshimura T, Ohtake Y, Ochiai K, Yokota J, Tanaka T: Allelic imbalance and mutations of the PTEN gene in ovarian cancer. Int J Cancer 2000, 85:160-165 [PubMed]
24. Obata K, Morland SJ, Watson RH, Hitchcock A, Chenevix-Trench G, Thomas EJ, Campbell IG: Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors. Cancer Res 1998, 58:2095-2097 [PubMed]
25. Whang YE, Wu X, Suzuki H, Reiter RE, Tran C, Vessella RL, Said JW, Isaacs WB, Sawyers CL: Inactivation of the tumor suppressor PTEN/MMAC1 in advanced human prostate cancer through loss of expression. Proc Natl Acad Sci USA 1998, 95:5246-5250 [PMC free article] [PubMed]
26. Dahia P, Fitzgerald M, Zhang X, Marsh D, Zheng Z, Pietsch T, von Deimling A, Haluska F, Haber D, Eng C: A highly conserved processed PTEN pseudogene is located on chromosome band 9p21. Oncogene 1998, 16:2403-2406 [PubMed]
27. Salvesen HB, MacDonald N, Ryan A, Jacobs IJ, Lynch ED, Akslen LA, Das S: PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma. Int J Cancer 2001, 91:22-26 [PubMed]
28. Weng LP, Smith WM, Dahia P, Ziebold U, Lees J, Eng C: PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G1 arrest followed by cell death. Cancer Res 1999, 59:5808-5814 [PubMed]
29. Li J, Simpson L, Takahashi M, Miliaresis C, Myers MP, Tonks N, Parsons R: The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene. Cancer Res 1998, 58:5667-5672 [PubMed]
30. Tamura M, Gu J, Matsumoto K, Aota S, Parsons R, Yamada KM: Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science 1998, 280:1614-1617 [PubMed]
31. Tamura M, Gu J, Takino T, Yamada KM: Tumor suppressor PTEN inhibition of cell invasion, migration, and growth: differential involvement of focal adhesion kinase and p130Cas. Cancer Res 1999, 59:442-449 [PubMed]
32. Liliental J, Moon SY, Lesche R, Mamillapalli R, Li D, Zheng Y, Sun H, Wu H: Genetic deletion of the Pten tumor suppressor gene promotes cell motility by activation of Rac1 and Cdc42 GTPases. Curr Biol 2000, 10:401-404 [PubMed]
33. Eng C: Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet 2000, 37:828-830 [PMC free article] [PubMed]
34. Podsypanina K, Ellenson LH, Nemes A, Gu J, Tamura M, Yamada KM, Cordon-Cardo C, Catoretti G, Fisher PE, Parsons R: Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems. Proc Natl Acad Sci USA 1999, 96:1563-1568 [PMC free article] [PubMed]
35. Stambolic V, Tsao MS, Macpherson D, Suzuki A, Chapman WB, Mak TW: High incidence of breast and endometrial neoplasia resembling human Cowden syndrome in pten+/− mice. Cancer Res 2000, 60:3605-3611 [PubMed]
36. Suzuki A, de la Pompa JL, Stambolic V, Elia AJ, Sasaki T, del BB I, Ho A, Wakeham A, Itie A, Khoo W, Fukumoto M, Mak TW: High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol 1998, 8:1169-1178 [PubMed]
37. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Ziebold U, Eng C: Changes in endometrial PTEN expression throughout the human menstrual cycle. J Clin Endocrinol Metab 2000, 85:2334-2338 [PubMed]
38. Parazzini F, La Vecchia C, Bocciolone L, Franceschi S: The epidemiology of endometrial cancer. Gynecol Oncol 1991, 41:1-16 [PubMed]
39. Weng LP, Smith WM, Brown JL, Eng C: PTEN inhibits insulin-stimulated MEK/MAPK activation and cell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model. Hum Mol Genet 2001, 10:605-616 [PubMed]
40. Ali IU: Gatekeeper for endometrium: the PTEN tumor suppressor gene. J Natl Cancer Inst 2000, 92:861-863 [PubMed]
41. Obata K, Hoshiai H: Common genetic changes between endometriosis and ovarian cancer. Gynecol Obstet Invest 2000, 50(Suppl 1):39-43 [PubMed]
42. Sato N, Tsunoda H, Nishida M, Morishita Y, Takimoto Y, Kubo T, Noguchi M: Loss of heterozygosity on 10q23.3 and mutation of the tumor suppressor gene PTEN in benign endometrial cyst of the ovary: possible sequence progression from benign endometrial cyst to endometrioid carcinoma and clear cell carcinoma of the ovary. Cancer Res 2000, 60:7052-7056 [PubMed]
43. Rubin MA, Gerstein A, Reid K, Bostwick DG, Cheng L, Parsons R, Papadopoulos N: 10q23.3 loss of heterozygosity is higher in lymph node-positive (pT2–3,N+) versus lymph node-negative (pT2–3,N0) prostate cancer. Hum Pathol 2000, 31:504-508 [PubMed]
44. Gimm O, Perren A, Weng LP, Marsh DJ, Yeh JJ, Ziebold U, Gil E, Hinze R, Delbridge L, Lees JA, Mutter GL, Robinson BG, Komminoth P, Dralle H, Eng C: Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors. Am J Pathol 2000, 156:1693-1700 [PMC free article] [PubMed]
45. Gray IC, Stewart LM, Phillips SM, Hamilton JA, Gray NE, Watson GJ, Spurr NK, Snary D: Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN. Br J Cancer 1998, 78:1296-1300 [PMC free article] [PubMed]
46. Dong JT, Sipe TW, Hyytinen ER, Li CL, Heise C, McClintock DE, Grant CD, Chung LW, Frierson HF: PTEN/MMAC1 is infrequently mutated in pT2 and pT3 carcinomas of the prostate. Oncogene 1998, 17:1979-1982 [PubMed]
47. Yokomizo A, Tindall DJ, Hartmann L, Jenkins RB, Smith DI, Liu W: Mutation analysis of the putative tumor suppressor PTEN/MMAC1 in human ovarian cancer. Int J Oncol 1998, 13:101-105 [PubMed]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology
PubReader format: click here to try


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...