• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

HMGI(Y) Gene Expression in Colorectal Cancer: Comparison with some Histological Typing, Grading, and Clinical Staging

Posted on: Tuesday, 13 January 2004, 06:00 CST

Summary

We investigated HMGI(Y) gene expression in 81 pairs of frozen samples obtained from colorectal carcinomas and adjacent normal colorectal mucosas and in four samples from colorectal mucosa from patients without neoplastic diseases. In this group, HMGI(T)- positive/-negative expression was compared with some histological features, grading, and clinical staging of neoplasms investigated to assess its potential role as a prognostic marker for colorectal cancer. Expression of HMGI(Y) gene was found in 51 of 81 cases of colorectal cancers, while, in normal mucosa, expression of this gene was not observed. HMGI(Y) gene expression was associated with more advanced tumors (T3, T4) and metastases to lymph nodes (N1, N2). The most interesting finding was that expression of this gene correlated with distant metastases. HMGI(Y) gene expression was detected in all cases classified as M1 (n = 19, p = 0.0008). We did not find any association between age, gender, tumor localization, histological type and this gene expression.

Key words: Colorectal cancer - HMGI(Y) gene

Introduction

The family of non-histone, high mobility group proteins [HMGI(Y)] consists of three proteins: HMGI (11.5 kDa), HMGY (10.4 kDa), and HMGI-C (12 kDa). The first two proteins are products of the same gene, HMGI(Y) (6p21) [15], generated through an alternative splicing of RNA transcripts [22, 23]. They differ from each other by 11 amino acids. The third one is encoded by a different gene (12q15) [7]. A characteristic feature of these proteins is the presence of three DNA binding domains called AT hooks, through which they bind to the minor groove of the DNA helix. They also have the ability to bind to bend, or distored DNA structures [17, 18, 27], which is the consequence of a high degree of intrinsic flexibility within AT hooks [29]. These features, connected with the ability to alter the structure of DNA substrates [67], allow them to function as architectural transcription factors, which can specifically interact with other transcriptional factors [12, 19, 20, 21, 36] in the positive and negative regulation of several gene activities [28]. The gene encoding HMGI(Y) protein is expressed at high levels during embryonic development [10], whereas, in adult tissues, it is not expressed or expressed at only very low levels [23, 26]. Also, the connection between HMGI(Y) protein overexpression and tumor phenotype has been demonstrated [16]. In four malignant tumors induced in mice by different experimental procedures (chemical, viral, or spontaneously derived), HMGI(Y) proteins were characteristic of transformed phenotype. It also has been demonstrated that overexpression of HMGI(Y) gene appears to be a common feature of malignant tumors [3, 5, 9, 33, 34, 35]. Rearrangement of this gene has been noted in human benign tumors of mesenchymal origin [24, 39]. It also has been demonstrated that HMGI(Y) gene expression was present both at the RNA and protein levels in human colorectal carcinoma cell lines and tissues. Conversely, no HMGI(Y) proteins have been detected in normal intestinal mucosa [13]. Using RT-PCR, it has been demonstrated that HMGI(Y) is expressed at a high percentage in colorectal cancer, in medium, in adenomatous polyps, but not in normal colon samples [25]. Another group [2] also has investigated HMGI(Y) gene expression at both the protein and mRNA levels in a limited panel of colorectal carcinomas, adenomas, and normal mucosa samples. Investigating 30 carcinoma cases, that group has determined correlations between the protein expression levels and various clinicopathological parameters such as depth of tumor invasion, regional lymph node metastasis, lymphatic and/or venous involvement, and Duke's stage. According to that group, expression of HMGI(Y) proteins was significantly increased in carcionoma and adenoma with severe atypia, compared with that in adenoma with less atypia and normal colorectal mucosa. Clinicopathological analysis has revealed that the level of HMGI(Y) protein expression was significantly correlated with poor prognosis in colorectal cancer patients.

The hitherto collected data, obtained by studying HMGI(Y) gene and protein expression in different neoplastically transformed cell lines and human neoplastic diseases, have led us to investigate the expression of HMGI(Y) gene in a separate population of Polish patients with colorectal cancer.

Materials and Methods

Tissues

Eighty-one pairs of tissue samples taken from the invasive front of colorectal carcinomas and adjacent normal colorectal mucosas obtained from patients operated on in the Oncological Center of Lodz, Poland, and four samples of normal colorectal mucosa from patients operated on because of abdominal injuries, were frozen in liquid nitrogen immediately after surgical resection and stored at - 80 C until processing.

Fig. 1. An example of multiplex PCR analysis of HMGI(Y) (93 bp) and [beta]-actine (168 bp) gene expression in colorectal cancer cases. PCR-negative control - 1, molecular size marker - 2, HMGZI(Y)- positive - 4 to 7 and negative cases - 3 and 8-10. As a PCR control, [beta]-actine gene was amplified in all analyzed cases.

RNA extraction

RNA was isolated by Total RNA Prep Plus Minicolumn Kit (A&A Biotechnology, Poland) based on an RNA isolation method developed earlier [11]. The isolated RNA has an A^sub 260/280^ ratio of 1.6- 1.8.

RT-PCR (Reverse transcriptase polimerase chain reaction)

cDNA was obtained by RevertAid(TM) cDNA Synthesis Kit (Fermentas, Lithuania). Reaction mixture containing total RNA (3 g), 1 l oligo(dT) 18 primer (0.5 g/l), and 6 l deionized, nuclease-free water was prepared. After mixing and spinning down, the mixture was incubated at 70 C for 5 min and then chilled on ice. After incubation, the following components were added: 4 l 5 reaction buffer, 1 l ribonuclease inhibitor (20 U/l), and 2 l 10 mM dNTP mix. This mixture was incubated at 37 C for 5 min. After incubation, 1 l RevertAid M-MuIV reverse transcriptase (200 U/L) was added. Finally, the mixture was incubated at 42 C for 60 min. The reaction was stopped by heating at 70 C for 10 min.

cDNA was amplified in 35 cycles using the cycle parameters' denaturation (94 C; 60 sec.), annealing (53 C; 60 sec.), extension (72 C; 30 sec.). PCR mixture contained 1.2 l 1.5 mM MgCl^sub 2^, 0.4 l 10 mM mix dNTPs, 0.2 l 0.5 U Taq Polymerase, 2 l 10 reaction buffer and 0.7 l 0.5 M of each primer. As a control, [beta]-actin gene was amplified. Sets of primers for HMGI(Y) were developed on the basis of the literature [8]. The PCR products were separated by electrophoresis on 2% agarose gel.

Statistics

Statistical analysis was made on the basis of the Chi-square test and the Chi-square test with Yate's correction.

Results

Eighty-one pairs of cases of colorectal carcinoma (invasive front) and corresponding healthy colorectal mucosas taken from the same patient, and 4 samples of colorectal mucosa from patients without colorectal neoplastic disease were examined. Fifty-one cases (63%) of carcinoma expressed HMGI(Y) gene, whereas the control mucosas and the mucosas obtained from patients without neoplastic disease did not.

The analyzed population consisted of 43 (53%) women (mean age 60.5 5) and 38 (47%) men (mean age 62.5 5). HMGI(Y) gene was expressed in 23 cases (53.5%) of carcinoma affecting women and in 28 cases (73.7%) of carcinoma affecting men. There was no statistically significant correlation between age, gender, and expression of HMGI(Y) gene.

The group investigated consisted of 35 cases of rectal carcinoma and 46 cases of colon carcinoma. The precise localization, the number of cases, in particular colon parts, and expression of HMGI(Y) are presented in Table 1. HMGI(Y) was expressed in 60% of rectal carcinomas and in 67% of other cases. This analysis also did not reveal any statistically significant correlation between HMGI(Y) expression and tumor localization.

Histologically, the carcinomas analyzed were classified as tubular adenocarcinoma, mucinous adenocarcinoma, and tubular adenocarcinoma with part of mucinous adenocarcinoma (mucinous adenocarcinoma occupies less than 50% of tumor size). Out of 60 tubular adenocarcinomas, 40 (66.6%) expressed HMGI(Y) gene. This gene also was expressed in 8 (73%) out of 11 mucinous adenocarcinomas and in three (30%) out of 10 tubular adenocarcinomas with part of mucinous adenocarcinoma.

For each carcinoma, the histological grade was determined. Thus, the neoplasms were divided into three groups. The low malignancy group consisted of 14 cases, 13 of which (92.8%) expressed the gene investigated. In the largest group of moderate malignancy cancers, 22 (57.8%) out of 38 cases were HMGI(Y)-positive; in the group of 28 cases with highly malignant neoplasms, 16 cases (57.1%) were HMGI(Y)- positive.

To assess the clinical utility of HMGI(Y) gene expression, our results were compared with several clinicopathological parameters such as depth of tumor invasion (T), lymph node metastases (N), distant metastases (M) (TNM classification), and Duke's classification.

The vast majority of cases investigated in this study (70%) belonged to the group with deep wall penetration (T3 and T4), whereas only 30% belonged to the T1 and T2 groups. Although HMGI(Y) was found to be expressedmore often in more advanced tumors (T3 and T4), there was no statistical significance between HMGI(Y) gene expression and the depth of tumor penetration (p = 0.57, Chi square test, Table 2)

Another parameter analyzed in this study was the expression of HMGI(Y) gene in cases with and without lymph node metastases. Twenty- eight (58.3%) out of 48 cases without invasion to lymph nodes expressed HMGI(Y) gene; however, among the cases with lymph node metastases (N1, N2), 23 (69.9%) out of 33 cases were HMGI(Y)- positive. These data also did not reveal any statistically significant correlation between HMGI(Y) gene expression and invasion to lymph nodes (p = 0.29, Chi square test, Table 3).

Table 1. Expression of HMGI(Y) gene and localization of primary colorectal carcinoma

Table 2. Expression of HMGI(Y) gene and depth of tumor invasion according to TNM classification

Table 3. Expression of HMGI(Y) gene and involvement of lymph nodes

Table 4. Expression of HMGI(Y) gene and distant metastases

Table 5. HMGI(Y) gene expression in particular stages of Dukes' classification

Table 6. Statistical dependency between HMGI(Y) gene expression and parameters analyzed

In all carcinomas with distant metastases (19 cases) was HMGI(Y) gene expression detected (p = 0.0008, Chi square test with Yates correction, Table 4).

Similar data were obtained after having compared HMGI(Y) gene expression with particular clinical stage according to Duke's classification (Table 5). Statistical dependencies are presented in Table 6.

Discussion

Colorectal cancer is one of the most frequent neoplastic human diseases. For this reason, it is very important to determine those factors that are engaged in its development. Proteins belonging to the HMGI(Y) family appear to play an important role in this process. Their overexpression has been found in neoplastically transformed cell lines and human neoplasms [3, 5, 9, 34, 35], including colon carcinomas [2]. In thyroid cancers, expression of HMGI(Y) is correlated with the malignant phenotype [9]. Its expression has been found only in thyroid carcinomas and thyroid carcinoma cell lines, but not in adenomas, goiters, and normal thyroid tissue. Similar data have been obtained for patients with prostate cancer, where a significant correlation between increased HMGI(Y) mRNA expression, and poor prognosis has been described [34]. HMGI(Y) has been reported to be strongly expressed in pancreatic carcinomas and can be useful in distinguishing between malignant and benign lesions [I]. Another study suggests that the determination of HMGI(Y) protein expression could be a potential diagnostic marker for the diagnosis of colorectal neoplasms and can be of great value in predicting the prognosis of patients with colorectal carcinomas [2]. The blocking of HMGI(Y) protein synthesis by an adenovirus carrying the HMGI(Y) gene in an antisense orientation (Ad-Yas) led to programmed cell death of two human thyroid anaplastic carcinoma cell lines (ARO and FB-1), but not in normal thyroid cells. The Ad-Yas virus has been reported to lead to death of lung, colon, and breast carcinoma cells both in vitro and in vivo, without interfering with the growth of normal cells [31]. This specificity is the consequence of differential expression of HMGI(Y) in normal and neoplastic cells. Although increased expression of HMGI(Y) proteins is associated with cellular proliferation and neoplastic transformation, the role of these proteins in the pathogenesis of malignancy remains unclear. Wood et al. [38] have demonstrated an interaction between the HMGI(Y) promoter and the oncoprotein c-Myc, indicating that HMGI(Y) is a direct c-Myc target gene. HMGI(Y) protein expression was stimulated by this oncoprotein in a Myc- estradiol receptor cell line and decreased in Mycdeficient fibroblasts. Expression of these proteins was also increased in Burkitt's lymphoma cell lines, which are known to have increased c- Myc protein. Injection of cells overexpressing HMGI(Y) induced tumors and distant metastases in nude mice [28, 37].

Analysis of the transcription profiles of cells employing cDNA arrays has demonstrated that overexpression of HMGI(Y) proteins modulates the expression of a complex set of genes responsible for signal transduction, cell proliferation, tumor initiation, migration, induction of angiogenesis, and colonization [28] These data support the hypothesis that overexpression of the HMGI(Y) proteins is associated with neoplastic transformation, metastatic progression, and mesenchymal transition of human breast epithelial cells in the context of an intact living organism.

In our study, we analyzed the expression of HMGI(Y) gene in colorectal carcinomas and normal colon mucosa. We did not detect HMGI(Y) expression in normal colon mucosa, which was in line with data obtained by other authors [2, 13, 25]. In colorectal cancers, HMGI(Y) gene expression has been detected in 63% of cases. These data, which are in accordance with those reported by others [2], indicate that HMGI(Y) gene plays an important role in colorectal carcinogenesis. Conversely, 37% of carcinomas without HMGI(Y) gene expression may suggest that the gene, despite its close association with neoplastic transformation of the cell, is not always required for this process, and the potential cancer gene therapy based on the suppression of HMGI(Y) protein synthesis may be efficient only in some cases.

Analysis of HMGI(Y) gene expression and its comparison with depth of tumor invasion and lymph node metastases (TNM classification) revealed that, in more advanced clinical stages, this gene is expressed more often; however, in fact, there is no statistically significant correlation between HMGI(Y) gene expression and these factors. A similar relationship between HMGI(Y) protein expression levels and immunohistochemistry as well as clinicopathological parameters has been observed in 30 carcinoma cases [2]. Eighteen (60%) of them showed high, nine (30%) showed moderate, and three (10%) exhibited HMGI(Y) expression at a low level. Fourteen of 17 (82.4%) invasion-positive cases showed high levels, whereas eight out of 11 (72.7%) invasion-negative cases showed low to moderate levels of HMGI(Y) protein expression. A significant correlation was detected between high-level of HMGI(Y) protein expression and the presence of lymph node metastases and advanced stage according to Duke's classification, which is connected with poor prognosis for patients with colorectal cancer [4, 14]. This study revealed a striking correlation between the level of HMGI(Y) protein expression and factors closely associated with poor prognosis for patients with colorectal cancer. Another group [26] also has analyzed HMGI(Y) gene expression in colorectal cancer and has evaluated its clinicopathological significance. In that study, HMGI(Y) gene expression was demonstrated by a competitive RT-PCR technique, and 63 out of 64 (98.4%) colorectal cancer samples and 2 out of 5 (40%) adenomatous polyps were positive, whereas 21 normal colon samples were negative. This study failed to show a correlation between prognostic factors in colorectal cancer such as age, sex, tumor size, histological grade, lymph node metastasis status, lymphatic invasion, angio-invasion [32] and HMGI(Y) gene expression levels.

The most interesting finding of our study was that all 19 cases of colorectal carcinoma with metastasis to distant organs expressed HMGI(Y) gene. Therefore, we suggest that HMGI(Y) may participate in growth- and differentiation-related tumor progression events of colorectal cancer. This finding supports the data regarding the important role of HMGI(Y) gene and proteins in metastatic tumor progression, resulting in a remarkable clinical progression of neoplastic diseases. Thirty-four HMGI(Y) gene-expressing cases without distant metastases can form a group with micrometastases that are not manifested clinically and should be monitored closely. Using the semi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), Sezer et al. [34] recently have demonstrated HMGI- C gene expression in the peripheral blood of patients with breast cancer. This expression was correlated with a poor prognosis for the patients. To date, data regarding HMGI(Y) expression in the peripheral blood have not been available. In future studies, we will determine the presence of the HMGI(Y) gene transcript in the peripheral blood of patients suffering from colon cancer. This may significantly contribute to an early detection of this disease and may improve the monitoring of patients after surgery.

Acknowledgements. The work was supported by grant 502-13-844 from the Medical University of Lodz, Poland. We wish to thank Prof. Ryszard Wierzbicki for his critical comments and Mrs. Anna Taczalska- Piekarska for her help in editing the text.

References

1. Abe N, Watanabe T, Izumisato Y, Masaki T, Mori T, Sugiyama M, Chiappetta G, Fusco A, Fujioka Y, Atomi Y (2002) Diagnostic significance of high mobility group I(Y) protein expression in intraductal papillary mucinous tumors of the pancreas. Pancreas 25: 198-204

2. Abe N, Watanabe T, Sugiyama M, Uchimura H, Chiappetta G, Fusco A (1999) Determination of high mobility group I(Y) expression level in colorectal neoplasias: a potential diagnostic marker. Cancer Res 59: 1169-1174

3. Bandiera A, Bonifacio D, Manfioletti G, Mantovani F, Rustighi A, Zanconati F, Fusco A, Di Bonito L, Giancotti V (1998) Expression of HMGI(Y) proteins in squamous intraepithelial and invasive lesions of the uterine cervix. Cancer Res 58: 426-431

4. Bosman FT (1995) Prognostic value of pathological characteristics of colorectal cancer. Eur J Cancer 31A: 1216-1221

5. Bussemakers MJ, van de Ven WJ, Debruyne FM, Schalken JA (1991) Identification of high mobility group protein I(Y) as potential progression marker for prostate cancer by differential hybridization analysis. Cancer Res 57:606-611

6. Bustin M, Reev\es R (1996) High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. Prog Nucleic Acid Res Mol Biol 54: 35-100

7. Chau KY, Patel UA, Lee KL, Lam HY, Crane-Robinson C (1995) The gene for the human architectural transcription factor HMGI-C consists of five exons each coding for a distinct functional element. Nucleic Acids Res 23: 4262-4266

8. Chiappetta GV, Avantaggiato R, Visconti M, Fedele S, Battista F, Trapasso BM, Merciai V, Fidanza V, Giancotti M, Santoro A, Simeone A, Fusco A (1996) Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma. Oncogene 13: 2439-2446

9. Chiappetta G, Tallini G, De Biasio MC, Manfioletti G, Martinez- Tello FJ, Pentimalli, F, de Nigris F, Mastro A, Botti G, Fedele M, Berger N, Santoro M, Giancotti V, Fusco A (1998) Detection of high mobility group I HMGI(Y) protein in the diagnosis of thyroid tumors: HMGI(Y) expression represents a potential diagnostic indicator of carcinoma. Cancer Res 58: 4193-4198

10. Chiappetta G, Avantaggiato V, Visconti R, Fedele M, Battista S, Trapasso F, Merciai BM, Fidanza V, Giancotti V, Santoro M, Simeone A, Fusco A (1996) High level expression of the HMGI(Y) gene during embryonic development. Oncogene13: 2439-2446

11. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinum thiocynate-phenolchloroform extraction. Analytical Biochem 162: 156-159

12. Currie RA (1997) Functional interaction between the DNA binding domain of NF-Y and the high mobility group protein HMG- I(Y). J Biol Chem 272: 30880-30888

13. Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, Casamassimi A, Santoro M, Giancontti V, Fusco A (1996) Human colorectal carcinomas express high levels of high mobility group HMGI(Y) proteins. Cancer Res 56: 1896-1901

14. Fielding LP, Pettigrew N (1995) College of American Pathologists Conference XXVI on clinical relevance of prognostic markers in solid tumor. Arch Pathol Lab Med 119: 1115-1121

15. Friedmann M, Holth LT, Zoghbi HY, Reeves R (1993) Organization, inducible-expression and chromosome localization of the human HMG-I(Y) nonhistone protein gene. Nucleic Acids Res 21: 4259-4267

16. Giancotti V, Buratti E, Perissin L, Zorzet S, Balmain A, Portella G, Fusco A, Goodwin GH (1989) Analysis of HMGI nuclear proteins in mouse neoplastic cells induced by different procedures. Exp Cell Res 184: 538-545

17. Hill DA, Reeves R (1997) Competition between HMGI(Y), HMG-I and histone Hl on four-way junction DNA. Nucleic Acids Res 25: 3523- 3531

18. Hill DA, Pedulla ML, Reeves R (1999) Directional binding of HMG-I(Y) on four-way junction DNA and the molecular basis for competitive binding with HMG-1 and histone H1. Nucleic Acids Res 27: 2135-2144

19. Himes SR, Coles LS, Reeves R, Shannon MF (1996) High mobility group protein I(Y) is required for function and for c-Rel binding to CD28 response elements within the GM-CSF and IL-2 promoters. Immunity 5: 479-489

20. Himes SR, Reeves R, Attema J, Nissen M, Li Y, Shannon MF (2000) The role of high-mobility group I(Y) proteins in expression of IL-2 and T cell proliferation. J Immunol 164:3157-3168

21. John S, Reeves RB, Lin J-X, Child R, Leiden JM, Thompson CB, Leonard WJ (1995) Regulation of cell-type-specific interleukin-2 receptor -chain gene expression: potential role of physical interactions between Elf-1, HMGI(Y), and NF-B family proteins. Mol Cell Biol 75: 1786-1796

22. Johnson KR, Lehn DA, Reeves R (1989) Alternative processing of mRNAs encoding mammalian chromosomal high-mobility-group proteins HMG-I and HMG-Y. Mol Cell Biol 9: 2114-2123

23. Johnson KR, Lehn DA, Elton TS, Barr PJ, Reeves R (1988) Complete murine cDNA sequence, genomic structure, and tissue expression of the high mobility group protein HMG-I(Y). J Biol Chem 263: 18338-18342

24. Kazmierczak B, Cin PD, Wanschura S, Bartnitzke S, Van der Berghe H, Bullerdiek J (1997) Cloning and molecular characterisation of part of a new gene fused to HMGIC in mesenchymal tumors. Am J Pathol 750: 901-910

25. Kim DH, Park YS, Park CJ, Son KC, Nam ES, Shin HS, Ryu, JW, Kim DS, Park CK, Park YE (1999) Expression of the HMGI(Y) gene in human colorectal cancer. Int J Cancer 84: 376-380

26. Lundberg K, Karlson JR, Ingebrigtsen K, Holtlund J, Lund T, Laland SG (1989) On the presence of the chromosomal proteins HMG-I and HMG-Y in rat organs. Biochim Biophys Acta 7009: 277-279

27. Nissen MS, Reeves R (1995) Changes in superhelicity are introduced into closed circular DNA by binding of high mobility group protein I/Y. J Biol Chem 270: 4355-4360

28. Reeves R, Edberg DD, Li Y (2001) Architectural trabscriptional factor HMGI(Y) promotes tumor progression and mesenchymal transition of human epithelial cells. Mol Cell Biol 21: 575-594

29. Reeves R, Nissen MS (1990) The A . T-DNA-binding domain of mammalian high mobility group I chromosomal proteins: a novel peptide motif for recognizing DNA structure. J Biol Chem 265: 8573- 8582

30. Rosai J, (1996) Ackerman's surgical pathology, vol. 1, pp. 775-777, Mosby, St. Louis

31. Scala S, Portella G, Fedele M, Chiappetta G, Fusco A (2000) Adenovirus-mediated suppression of HMGI(Y) protein synthesis as potential therapy of human malignant neoplasias. Proc Natl Acad Sci USA 97: 4256-4261

32. Sezer O, Langelotz C, Blohmer JU, Smchid P, Akrivakis K, Possinger K (2000) Detection of HMGI-C in the peripheral blood of breast cancer patients. Eur J Cancer 36: 1944-1948

33. Tallini G, Dal Cin P (1999) HMGI(Y) and HMGI-C dysregulation: a common occurrence in human tumors. Adv Anat Pathol 6: 237-246

34. Tamimi Y, van der Poel HG, Karthaus HF, Debruyne FM, Schalken JA (1996) A retrospective study of high mobility group protein I(Y) as a progression marker for prostate cancer determined by in situ hybridization. Br J Cancer 74: 573-578

35. Tamimi Y, van der Poel HG, Denyn M, Umbas R, Karthaus HF, Debruyne FM, Schalken JA (1993) Increased expression of high mobility group protein I(Y) in high grade prostate cancer determined by in situ hybridization. Cancer Res 53: 5512-5516

36. Thanos D, Maniatis T (1992) The high mobility group protein HMG-I(Y) is required for NF- B-dependent virus induction of the human interferon-beta gene. Cell 77: 777-789

37. Wood LJ, Maher JF, Bunton TE, Resar LMS (2000) The oncogenic properties of the HMG-I gene family. Cancer Res 60: 4256-4261

38. Wood LJ, Mukherjee M, Dolde CE, Xu Y, Maher JF, Bunton TE, Williams JB, Resar LMS (2000) HMG-I/Y, a new c-Myc target gene and potential oncogene. Mol Cell Biol 20: 5490-5502

39. Xiao S, Lux ML, Reeves R, Hudson TJ, Fletcher JA (1997) HMGI(Y) activationby chromosome 6p21 rearrangements in multilineage mesenchymal cells from pulmonary hamartoma. Am J Pathol 752: 431- 435

Received: February 3, 2003

Acceped in revised version: September 3, 2003

M. Balcerczak1, G. Pasz-Walczak2, E. Balcerczak1, M. Wojtylak1, R. Kordek2, M. Mirowski1

1 Department of Pharmaceutical Biochemistry, Molecular Biology Laboratory, Lodz, Poland 2 Department of Tumor Pathology, Medical University, Lodz, Poland

Address for correspondence: Marek Mirowski, Department of Pharmaceutical Biochemistry, Molecular Biology Laboratory, Faculty of Pharmacy, Medical University, Muszynskiego 1 Street, 90-151 Lodz, Poland.

Phone/Fax: +48 42 677-91-30.

E-mail: mirowski@ich.pharm.am.lodz.pl

Copyright Urban & Fischer Verlag 2003

More News in this Category