Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Watanabe, M.
Right arrow Articles by Nagao, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, M.
Right arrow Articles by Nagao, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Japanese Journal of Clinical Oncology Pages 389-393

Genetic Alterations of Androgen Receptor Gene in Japanese Human Prostate Cancer
Introduction
Materials and Methods
   Tissue Samples
   DNA Extraction
   Analysis of AR Gene Mutations
   DNA Sequencing
Results
   Screening of AR Gene Mutations by PCR-SSCP Analysis
   Sequencing
   Clinicopathological Correlation
Discussion
Acknowledgments
References
Genetic Alterations of Androgen Receptor Gene in Japanese Human Prostate Cancer

Genetic Alterations of Androgen Receptor Gene in Japanese Human Prostate Cancer

Masatoshi Watanabe1,2, Toshikazu Ushijima1, Taizo Shiraishi2, Ryuichi Yatani2, Jun Shimazaki3, Toshihiko Kotake4, Takashi Sugimura1, Minako Nagao1

1Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, 2Second Department of Pathology, School of Medicine, Mie University, Mie, 3Department of Urology, School of Medicine, Chiba University, Chiba and 4Department of Urology, Center for Adult Diseases, Osaka, Japan

In order to determine the significance of androgen receptor (AR) gene mutations for Japanese prostate cancers, we examined the entire coding region, from exon A to H, in 36 primary lesions. Five in stage A, 12 in stage B, six in stage C and 13 in stage D were subjected to PCR-SSCP analysis for genomic DNA and nucleotide sequencing. Mutations were detected in five samples (14%). Two in stage D and refractory to anti-androgen treatment showed mis-sense mutations. The other three showed changes in the length of the CAG repeat in exon A, with an expansion or a contraction of one repeat unit. However, no association with changes in AR function was indicated because they had not been refractory to hormone therapy. Since these latter three tumors were associated with microsatellite instability, the changes might have been the result of an impairment of mismatch repair. This study indicates that AR gene mutations play a role, in only a subset of prostate cancer patients, in a treatment-refractory state.

Key words: androgen receptor gene - CAG repeats - prostate cancer - refractory to hormone therapy

Introduction

Prostate cancer is the most common cancer in American men (1) and lately its incidence has been increasing in Japan (2). It has been established that androgen is necessary for both the growth and differentiation of the prostate gland (3). One useful therapeutic approach is therefore anti-androgen treatment and this has proved temporarily effective in bringing about remission of prostate cancer (4). However, in most cases recurrence occurs in association with acquired resistance to anti-androgen drugs. It is therefore very important that the mechanisms involved be clarified (4). Interestingly, although growth of the LNCaP human prostate cancer cell line is usually androgen independent, it can be stimulated by androgen, estrogen or anti-androgen treatment. This cell line has a point mutation at codon 877 of the androgen receptor (AR) gene, which is located within the steroid binding site and changes the steroid specificity (5,6). Such mutations could therefore be involved in the mechanisms underlying prostate cancer becoming refractory after hormonal therapy.

Changes in the CAG repeat number in the AR gene, as reported in neural disease, might also be important. The expansion of CAG repeats in spinal and bulbar muscular atrophy (SBMA) has been well documented (7) and Huntington's disease (HD), dentatorubral and pallidoluysian atrophy (DRPLA) and spinocerebellar ataxia type I result from a trinucleotide repeat expansion (8,9). Contraction of CAG repeats in the AR gene has in fact already been described (10) in human prostate cancers.

To clarify the role of AR mutations in progression and/or the refractory state, we therefore examined 36 Japanese prostate cancers for mutations in the entire coding region by PCR-SSCP analysis and nucleotide sequencing of exons A-H.

Materials and Methods

Tissue Samples

Samples of 36 prostate tumors were collected from 36 patients who visited Mie University Hospital, Chiba University Hospital and the Osaka Center for Adult Disease between 1991 and 1993. The age of the patients ranged from 42 to 83 years old with a median of 69 years. All 36 samples were of primary prostate tumors and were obtained by radical prostectomy (21 cases), radical cystoprostectomy of bladder tumors (two cases) and autopsy (13 cases).

Table 1 . Clinicopathological features of the examined prostate cancer
Sample Age of
patient		 State Histological
grade		 Gleason
score		 Refratory to
hormone therapy
1 64 A W 3 -
2 72 A W 3 -
3 76 A W 4 -
4 78 A P 8 -
5 45 A P 9 -
6 63 B M 6 -
7 58 B M 6 -
8 70 B M 5 -
9 64 B M 5 -
10 65 B M 6 -
11 57 B M 7 -
12 73 B M 6 -
13 66 B M 5 -
14 82 B M 7 -
15 57 B P 8 -
16 72 B P 7 -
17 65 B P 9 -
18 63 C W 5 -
19 64 C M 5 -
20 73 C M 6 -
21 73 C M 6 -
22 61 C M 6 -
23 67 C P 8 -
24 67 D W 5 +
25 77 D M 7 +
26 73 D M 7 +
27 65 D M 8 +
28 71 D P 7 +
29 75 D P 9 +
30 75 D P 9 +
31 42 D P 9 +
32 66 D P 9 +
33 80 D P 9 +
34 83 D P 9 +
35 83 D P 9 +
36 78 D P 10 +
Average 66.5     6.9  
W, well differentiated; M, moderately differentiated; P, poorly differentiated.

The samples were immediately frozen after resection and kept at -80°C until use. Sections of the frozen samples were subjected to light microscopic review after hematoxylin-eosin staining by a pathologist experienced in the diagnosis of prostate cancer and normal tissues were removed to obtain material containing more than 75% tumor cells for DNA extraction.

All samples were staged and graded according to the General Rules for Clinical and Pathological Studies on Prostatic Cancer using the Gleason system of classification (10,11). Table 1 summarizes the clinical information for all the prostate tumor cases.

DNA Extraction

Genomic DNA was extracted from frozen tissues by standard procedures using proteinase K digestion, serial phenol and chloroform extractions and ethanol precipitation (12).

Analysis of AR Gene Mutations

Eleven sets of primers were prepared to amplify DNA fragments covering exons A-H of the AR gene, mostly based on reported sequences (Table 2) (10,14), with a DNA synthesizer (Applied Biosystems, Foster City, CA, USA). The primers for exons A1, A3, A4, A5, A6, A7, B1, B2, C1, C2 and D1 were newly designed to obtain shorter PCR products. Primers were end-labeled with [[gamma]-32P]ATP using T4 polynucleotide kinase (Takara, Kyoto, Japan). Aliquots of 50 ng of genomic DNA were amplified by PCR in 5 µl of reaction mixture, which consisted of 80 nM end-labeled 5 and 3 primers, 100 µM of each of dNTP, 10 mM Tris-Cl (pH 8.3), 50 mM KCl, 1.5 mM MgCl2, 0.001% gelatin and 0.1 U/µl of Taq DNA polymerase (Perkin-Elmer Cetus, Norwalk, CT, USA). The reaction conditions were 94°C (0.5 min), 55°C (0.5 min) and 72°C (1 min) for 35 cycles. The reaction was initiated by a 3 min incubation at 94°C and finished with 7 min at 72°C. A 5 µl volume of PCR products was added to 45 µl of loading buffer (95% formamide, 20 mM EDTA, 0.05% bromophenol blue and 0.05% xylene cyanol), heat denatured and 1 µl portions were loaded into lanes of 4.9% polyacrylamide gels, with or without 5% glycerol. Electrophoresis was carried out at 40 W and 18°C with a water-jacket. Gels were then dried and exposed to XAR-5 (Kodak, Rochester, NY, USA) at -80°C for 0.5-1 h.

Table 2 . The newly designed PCR primer sets for the androgen receptor gene
Exon Sense primer Antisense primer
A1 5[prime]-GAGAAGGGGAGGCGGGGTAA-3[prime] 5[prime]-CTGCAGCAGCAGCAAACTGG-3[prime]
A3 5[prime]-CAGCAGGGTGAGGATGGTTC-3[prime] 5[prime]-CTTTAAGGTCAGCGGAGCAG-3[prime]
A4 5[prime]-GACTCAGCTGCCCCATCCAC-3[prime] 5[prime]-TGCTCCAACHCCTCCACACC-3[prime]
A5 5[prime]-GGCACTTCGACCATTTCTGA-3[prime] 5[prime]-AGACAGGGTAGACGGCAGTT-3[prime]
A6 5[prime]-AGGGAGCTCCGGGACACTTG-3[prime] 5[prime]-TTCGGCTGTGAAGAGAGTGT-3[prime]
A7 5[prime]-CACCCTCAGCCGCCGCTTCC-3[prime] 5[prime]-CCTGGGCCGAAAGGCGACAT-3[prime]
B1 5[prime]-CTGCAGGTTAATGCTGAAGA-3[prime] 5[prime]-CCATAGTGACACCCAGAAGC-3[prime]
B2 5[prime]-ACCTGCCTGATCTGTGGAGA-3[prime] 5[prime]-GCCAATGACTCTATTTCTGA-3[prime]
C1 5[prime]-GTTTGGTGCCATACTCTGTC-3[prime] 5[prime]-TCCTTCGGAATTTATCAATA-3[prime]
C2 5[prime]-CTCCCAGGGAAACAGAAGTA-3[prime] 5[prime]-GTTGCCTATGAAAGGGTCAG-3[prime]
D1 5[prime]-TGTTTTTGACCACTGATGAT-3[prime] 5[prime]-CAGAAAGATGGGCTGACATT-3[prime]

Table 3 . Summary of the androgen receptor gene mutations
Sample No. Stage Histology Mutation
      Exon Codon Type A.A. change
4 A P A   (CAG)21 to (CAG)22* + Gly
18 C W A   (CAG)23 to (CAG)22 - Gly
29 D P A   (CAG)21 to (CAG)22 + Gly
30 D P D Codon 701 CTC to CAC Leu to His
34 D P H Codon 910 AAA to AGA Lys to Arg
*The CAG repeat starts from codon 58.

DNA Sequencing

DNA was extracted from shifted bands obtained by PCR-SSCP analysis. Fragments were directly subcloned into the pCR vector using a TA cloning system kit (Invitrogen, San Diego, CA, USA) and sequenced by the Sanger dideoxynucleotide method with a Sequenase Ver. 2.0 kit (United States Biochemical, Cleveland, OH, USA).

Results

Screening of AR Gene Mutations by PCR-SSCP Analysis

The labeled PCR products from pairs of tumor and non-tumor DNA samples were analyzed by electrophoresis. Five of the 36 prostate cancers showed mobility shifts. Samples 4, 18 and 29 showed a band shift in exon A (Fig. 1), sample 30 in exon D (Fig. 1) and sample 34 in exon H (Fig. 1). Samples 4 and 29 showed the same band shift.


Figure 1 PCR-SSCP analysis of AR gene mutations in prostate cancer. Sample numbers are shown above each panel. The samples were analyzed on 5% acrylamide gels with 5% glycerol. (A) Exon A: samples 4, 18 and 29 have shifted bands as compared with their respective normal tissues (4N, 18N and 29N). (B) Exon D: sample 30 has an abnormal band. (C) Exon H: sample 34 has an abnormal band.

Sequencing

The PCR products of all five samples showing band shifts in the SSCP analysis were subcloned and sequenced (Fig. 2). For each sample, sequences of 10 clones were determined. Mutations were detected in more than four clones of all the samples analyzed. Sample 30 had a CTC to CAC mutation at codon 701 in exon D. Sample 34 had an AAA to AGA mutation at codon 910 in exon H. Samples 4, 18 and 29 had changes in the CAG repeat number in exon A, as compared with that in normal tissue. Samples 4 and 29 had an increase in number; (CAG)21 to (CAG)22; 18 had a decrease; (CAG)23 to (CAG)22.


Figure 2 Results of sequence analyses. Sample numbers are indicated below each panel. Nucleotide changes were detected in sample 30 at codon 701 and in sample 34 at codon 910. The number of CAG repeat was decreased from 23 to 22 in sample 18, whereas it was increased from 21 to 22 in sample 4.

Clinicopathological Correlation

The data for AR gene mutations are summarized in Table 3. Mis-sense mutations were detected in two stage D cancers which were refractory to treatment. The increases in CAG repeats in exon A were detected in one stage A and one stage D cancer. The decrease was found in a stage C cancer. The lengths of the CAG repeats in these three cases were within the reported range of polymorphic variation for healthy people (15).


Discussion

Androgen acts on its target cells by binding to AR, causing transformation into a DNA-binding form that can interact with hormone responsive genes (16). The AR gene is located on the X chromosome and is composed of 8(A-H) coding exons. Exon A encodes a peptide encompassing 58% of the AR protein, the 917-amino acid protein having a DNA binding domain at the N-terminus and a steroid binding domain at the C-terminus (17). Mutations in the AR gene are known to cause androgen insensitivity syndrome (AIS) in males (18). So far, 65 different amino acid substitutions between amino acids 664 and 913 have been described (19).

The concept of androgen dependence of prostate cancer is based on the fact that a dramatic reduction in tumor mass is acheived after surgical castration or estrogen therapy. The development and progression of cancer in the prostate therefore appear to be androgen dependent. However, after androgen deprivation treatment, this androgen dependence is lost in most cases and progression to a more malignant status occurs. Qualitative and/or quantitative abnormalities in the AR gene may be involved in this phenomenon, hence information relating to AR expression levels and genetic alterations in prostate cancer is important.

Several studies on mutations in the AR gene in human prostate cancer have already been reported. Gaddipati et al. (14) found that 25% of advanced lesions had a mutation at codon 877, which lies within the hormone-binding domain. This was the same as that detected in LNCaP. Further, Tilley et al. (20), in Australia, detected a high rate of AR gene mutation in primary stage C and stage D prostate cancer prior to initiation of hormone therapy, 50% of these mutations being in exon A. On the other hand, a low incidence of AR gene mutation was reported in the UK (21), although the entire coding region of the AR gene was examined. With regard to mutations in the AR gene in Japanese prostate cancer, there have been two reports; one concerned with clinical and the other with latent cancer. Only one out of eight (12.5%) Japanese prostate cancer anti-androgen therapy-resistant cases was found to be positive, the primary tumor having a mutation at codon 701 in exon D, with an additional mutation at codon 877 in exon H in a lymphnode metastasis (22). Furthermore, while 23% of latent prostate cancers were found to exhibit mutations, the figure was zero for clinical lesions (23). Using PCR-SSCP analysis, exons B-H of the AR gene were analyzed in these two groups.

In this study, we analyzed mutations along the entire coding region of the AR gene for 36 prostate tumors in stages A-D and found two significant mutations (5%) in stage D refractory cases. Since 13 cases were refractory, only 15% of refractory cancers were demonstrated to be associated with AR gene mutations. Hence the available data suggest that the frequency of AR gene mutation is low in Japanese prostate cancer cases. The one mutation at codon 910 which was found in this study has not been reported previously, although the one at codon 701 was already known from studies of AIS patients and also prostate cancer, as noted above. Although the androgen-binding ability of the two mutants identified remains to be clarified, the prostate cancers harboring these mutations were found to become androgen independent after anti-androgen therapy.

As for the number of CAG repeats in the AR gene, Schoenberg et al. (10) reported a contraction of CAG repeats in a prostate cancer case which showed a paradoxical agonistic response to hormone therapy with an anti-androgen flutamide. It has been reported that an expansion of CAG repeats causes a linear decrease in the transactivation function of the AR protein, even though they are not included in the DNA-binding domain (24). In the present study, three cases demonstrated changes in the number of CAG repeats in the AR gene, two with an increase of one and one with a contraction of one. Since the length of the CAG repeat region varies within a range of about 17-29 in normal individuals, the significance of these `mutations' is unclear. Since all three cases were associated with microsatellite instability (M.Watanabe et al., unpublished results), the changes in the number of CAG repeats may have been the result of an impairment of mismatch repair.

Immunohistochemical studies have demonstrated that prostate cancers may contain both AR-positive and AR-negative malignant cells, even before androgen withdrawal therapy (25,26). It is therefore unclear whether alterations in the expression levels of the AR gene contribute to the progression of human prostate cancers to AR independence. In addition, Visakorpi et al. (27) recently reported high-level AR amplification in 30% of recurrent prostate cancers after hormone therapy, suggesting that this might enable prostate cancer cells to grow in an environment having a low concentration of androgen (27). Hence it is plausible that AR gene amplification could in fact be a major cause of the refractory state in Japanese prostate cancer. This possibility clearly warrants further attention.

Acknowledgments

This work was supported by a Grant-in-Aid from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control, Japan, and a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture.

References

1 Carter HB, Coffey DS. The prostate: an increasing medical problem. Prostate 1991;16:39-48.

2 Statistics and Information Department, Ministry of Health and Welfare. Vital Statistics 1991 Japan. Health and Welfare Statistics Association: Tokyo, 1993;266-71.

3 Coffey DS. The molecular biology, endocrinology and physiology of the prostate and seminal vesicles. In: Walsh PC, Retik AB, Stamey TA, Vaughan ED, editors. Campbell's Urology, Vol. I. W.B.Saunders: Philadelphia, 1992;221-66.

4 Isaacs JT, Coffey DS. Adaptation versus selection as the mechanism responsible for the relapse of prostatic cancer to androgen ablation therapy as studied in the Dunning R-3327H adenocarcinoma. Cancer Res 1981;41:5070-5. MEDLINE Abstract

5 Lubahn DB, Brown TR, Simental JA, Higgs HN, Migeon CJ, Wilson EM,et al. Sequence of the intron/exon junctions of the coding region of the human androgen receptor gene and identification of a point mutation in a family with complete androgen insensitivity. Proc Natl Acad Sci USA 1989;86:9534-8. MEDLINE Abstract

6 Veldscholte J, Ris-Stalpers C, Kuiper GGJM, Jenster G, Berrevoets C, Claassen E,et al. A mutation in the ligand binding domain of the androgen receptor of human LNCaP cells affects steroid binding characteristics and response to anti-androgens. Biochem Biophys Res Commun 1990;174:534-40.

7 Spada ARL, Wilson EM, Lubahn DB, Harding AE, Fiscbeck KH. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991;352:77-9.

8 Caskey CT, Pizzuti A, Fu Y-H, Fenwick RG, Nelson DL. Triplet repeat mutations in human disease. Science 1991;256:784-8.

9 Miwa S. Triplet repeats strike again. Nature Genet 1994;6:3-4. MEDLINE Abstract

10 Schoenberg MP, Hakini JM, Wang S, Bova GS, Epstein JI, Fiscbeck KH,et al. Microsatellite mutation (CAG24Æ18) in the androgen receptor gene in human prostate cancer. Biochem Biophys Res Commun 1994;198:74-80. MEDLINE Abstract

11 Japanese Urological Association and the Japanese Pathological Society. General Rule for Clinical and Pathological Studies on Prostate Cancer, 2nd ed. Tokyo: Kanehara Press, 1992;40-6 (in Japanese).

12 Gleason DF, Mellinger GT. Prediction of prognosis for prostatic adenocarcinoma by combined histologic grading and clinical staging. J Urol 1974;111:58-64. MEDLINE Abstract

13 Sambrook J, Fritsch EF, Maniatis T. Isolation of high-molecular-weight DNA from mammalian cells. In: Ford NNC, Ferguson M, editors, Molecular Cloning. A Laboratory Manual. New York: Cold Spring Harbor Laboratory Press, 1989;9.14-9.23.

14 Gaddipati JP, Mcleod DG, Heidenberg HB, Sesterhenn IA, Finger MJ, Moul JW,et al. Frequent detection of codon 877 mutation in the androgen receptor gene in advanced prostate cancers. Cancer Res 1991;54:2861-4.

15 Yamamoto Y, Kawai H, Nakahara K, Osame M, Nakatsuji Y, Kishimoto T, et al. A novel primer extension method to detect the number of CAG repeats in the androgen receptor gene in families with X-linked spinal and bulbar muscular atrophy. Biochem Biophys Res Commun 1992;182:507-13. MEDLINE Abstract

16 Beato M. Gene regulation by steroid hormones. Cell 1989;56:335-44. MEDLINE Abstract

17 Simental JA, Sar M, Lane MV, French FS, Wilson EM. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 1991;266:510-8. MEDLINE Abstract

18 Brown CJ, Goss SJ, Lubahn DB, Joseph DR, Wilson EM, French FS,et al. Androgen receptor locus on the human X chromosome: Regional localization to Xq11-12 and description of a DNA polymorphism. Am J Hum Genet 1989;44:264-9. MEDLINE Abstract

19 Patterson MN, Hughes IA, Gottlich B, Pinskyl L. The androgen receptor gene mutations database. Nucleic Acids Res 1994;22:3560-2. MEDLINE Abstract

20 Tilley WD, Buchanan G, Hickey TE, Bentel JM. Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res 1996;2:277-85.

21 Evans BAJ, Harper ME, Daniells CE, Watts CE, Matenhelia S, Green J,et al. Low incidence of androgen receptor gene mutations in human prostatic tumors using single strand conformation polymorphism analysis. Prostate 1996;28:162-71.

22 Suzuki H, Sato N, Watabe Y, Masai M, Seino S, Shimazaki J. Androgen receptor gene mutations in human prostate cancer. J Steroid Biochem Mol Biol 1993;46:759-65. MEDLINE Abstract

23 Takahashi H, Furusato M, Allsbrook WC JR, Nishii H, Wakui S, Barrett JC, et al. Prevalence of androgen receptor gene mutations in latent prostatic carcinomas from Japanese men. Cancer Res 1995;55:1621-4. MEDLINE Abstract

24 Chaberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 1994;22:3181-6.

25 Van der Kwast TH, Schalken J, De Winter JAR, Van Vroonhoven CCJ, Mulder E, Boersma W,et al. Androgen receptors in endocrine-therapy-resistant human prostate cancer. Int J Cancer 1991;48:189-93. MEDLINE Abstract

26 Sadi MV, Walsh PC, Barrack ER. Immunohistochemical study of androgen receptors in metastatic prostate cancer. Cancer 1991;67:3057-64. MEDLINE Abstract

27 Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Keinanen R, Palmberg C, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nature Genet 1995;9:401-6. MEDLINE Abstract

Received February 14, 1997; accepted June 9, 1997
For reprints and all correspondence: Minako Nagao, Carcinogenesis Division, National Cancer Center Research Institute, National Cancer Center, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan
Abbreviations: AR, androgen receptor; SBMA, spinal and bulbar muscular atrophy; HD, Huntington's disease; DRPLA, dentatorubral and pallidoluysian atrophy; AIS, androgen insensitivity syndrome

This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 19 May 1998
Copyright© Japanese Journal of Clinical Oncology, 1997.
This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 19 May 1998
Copyright© Japanese Journal of Clinical Oncology, 1997.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
M. P. Zeegers, L. A.L.M. Kiemeney, A. M. Nieder, and H. Ostrer
How Strong Is the Association Between CAG and GGN Repeat Length Polymorphisms in the Androgen Receptor Gene and Prostate Cancer Risk?
Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1765 - 1771.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
G. Buchanan, M. Yang, A. Cheong, J. M. Harris, R. A. Irvine, P. F. Lambert, N. L. Moore, M. Raynor, P. J. Neufing, G. A. Coetzee, et al.
Structural and functional consequences of glutamine tract variation in the androgen receptor
Hum. Mol. Genet., August 15, 2004; 13(16): 1677 - 1692.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
D. J. Lamb, E. Puxeddu, N. Malik, D. L. Stenoien, R. Nigam, G. Y. Saleh, M. Mancini, N. L. Weigel, and M. Marcelli
Molecular Analysis of the Androgen Receptor in Ten Prostate Cancer Specimens Obtained Before and After Androgen Ablation
J Androl, March 1, 2003; 24(2): 215 - 225.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. V. Krishnan, X.-Y. Zhao, S. Swami, L. Brive, D. M. Peehl, K. R. Ely, and D. Feldman
A Glucocorticoid-Responsive Mutant Androgen Receptor Exhibits Unique Ligand Specificity: Therapeutic Implications for Androgen-Independent Prostate Cancer
Endocrinology, May 1, 2002; 143(5): 1889 - 1900.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Buchanan, N. M. Greenberg, H. I. Scher, J. M. Harris, V. R. Marshall, and W. D. Tilley
Collocation of Androgen Receptor Gene Mutations in Prostate Cancer
Clin. Cancer Res., May 1, 2001; 7(5): 1273 - 1281.
[Abstract] [Full Text]

Home page
 Cancer Res.Home page
M. Marcelli, M. Ittmann, S. Mariani, R. Sutherland, R. Nigam, L. Murthy, Y. Zhao, D. DiConcini, E. Puxeddu, A. Esen, et al.
Androgen Receptor Mutations in Prostate Cancer
Cancer Res., February 1, 2000; 60(4): 944 - 949.
[Abstract] [Full Text]

Home page
 Mol. Endocrinol.Home page
L. V. Nazareth, D. L. Stenoien, W. E. Bingman III, A. J. James, C. Wu, Y. Zhang, D. P. Edwards, M. Mancini, M. Marcelli, D. J. Lamb, et al.
A C619Y Mutation in the Human Androgen Receptor Causes Inactivation and Mislocalization of the Receptor with Concomitant Sequestration of SRC-1 (Steroid Receptor Coactivator 1)
Mol. Endocrinol., December 1, 1999; 13(12): 2065 - 2075.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (25)
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Watanabe, M.
Right arrow Articles by Nagao, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Watanabe, M.
Right arrow Articles by Nagao, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?