Abstract
Rb2/p130 is a member of the retinoblastoma family of proteins, consisting of Rb, Rb2 and p107, which are important negative regulators of cell cycle progression and differentiation. While Rb2 downregulation was observed in several malignant tumours including endometrial cancer, the role of p130 in breast carcinomas is still unknown. We investigated Rb2 protein expression in tumour tissue from 68 mammary and 41 endometrial carcinomas, 4 mammary cell lines, and normal tissue samples. Therefore, we performed Western blot experiments for Rb2, Rb, and the oestrogen and progesterone receptors (ER, PR-A, PR-B). Weak or absent Rb2 expression was more often found in endometrial (59%) than in mammary carcinomas (24%). We found significant positive correlations of Rb2 expression with Rb, ER, and PR-B in breast cancer samples, and of Rb2 with Rb, PR-A, PR-B, and younger age in endometrial carcinomas. No significant associations with histological grading, stage, nodal involvement, or Ki67 staining were detected. Rb2 mRNA expression was studied by semi-quantitative RT-PCR in 56 endometrial or mammary tissue samples and correlated significantly with Western blot results. Our results indicate that loss of Rb2 expression, mostly by transcriptional down-regulation, may be associated with the development and dedifferentiation of most endometrial and a subset of mammary carcinomas. © 2001 Cancer Research Campaign http://bjcancer.com
Keywords: retinoblastoma protein family, oestrogen receptor, progesterone receptor, mammary carcinoma, endometrial carcinoma
Full Text
The Full Text of this article is available as a PDF (76.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baldi A., Esposito V., De Luca A., Fu Y., Meoli I., Giordano G. G., Caputi M., Baldi F., Giordano A. Differential expression of Rb2/p130 and p107 in normal human tissues and in primary lung cancer. Clin Cancer Res. 1997 Oct;3(10):1691–1697. [PubMed] [Google Scholar]
- Baldi A., Esposito V., De Luca A., Howard C. M., Mazzarella G., Baldi F., Caputi M., Giordano A. Differential expression of the retinoblastoma gene family members pRb/p105, p107, and pRb2/p130 in lung cancer. Clin Cancer Res. 1996 Jul;2(7):1239–1245. [PubMed] [Google Scholar]
- Claudio P. P., Howard C. M., Baldi A., De Luca A., Fu Y., Condorelli G., Sun Y., Colburn N., Calabretta B., Giordano A. p130/pRb2 has growth suppressive properties similar to yet distinctive from those of retinoblastoma family members pRb and p107. Cancer Res. 1994 Nov 1;54(21):5556–5560. [PubMed] [Google Scholar]
- Claudio P. P., Howard C. M., Fu Y., Cinti C., Califano L., Micheli P., Mercer E. W., Caputi M., Giordano A. Mutations in the retinoblastoma-related gene RB2/p130 in primary nasopharyngeal carcinoma. Cancer Res. 2000 Jan 1;60(1):8–12. [PubMed] [Google Scholar]
- Helin K., Holm K., Niebuhr A., Eiberg H., Tommerup N., Hougaard S., Poulsen H. S., Spang-Thomsen M., Norgaard P. Loss of the retinoblastoma protein-related p130 protein in small cell lung carcinoma. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6933–6938. doi: 10.1073/pnas.94.13.6933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard C. M., Claudio P. P., Gallia G. L., Gordon J., Giordano G. G., Hauck W. W., Khalili K., Giordano A. Retinoblastoma-related protein pRb2/p130 and suppression of tumor growth in vivo. J Natl Cancer Inst. 1998 Oct 7;90(19):1451–1460. doi: 10.1093/jnci/90.19.1451. [DOI] [PubMed] [Google Scholar]
- Lai H. C., Sun C. A., Yu M. H., Chen H. J., Liu H. S., Chu T. Y. Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types. Int J Cancer. 1999 Dec 22;84(6):553–557. doi: 10.1002/(sici)1097-0215(19991222)84:6<553::aid-ijc2>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
- Leoncini L., Bellan C., Cossu A., Claudio P. P., Lazzi S., Cinti C., Cevenini G., Megha T., Laurini L., Luzi P. Retinoblastoma-related p107 and pRb2/p130 proteins in malignant lymphomas: distinct mechanisms of cell growth control. Clin Cancer Res. 1999 Dec;5(12):4065–4072. [PubMed] [Google Scholar]
- Li S. F., Shiozawa T., Nakayama K., Nikaido T., Fujii S. Stepwise abnormality of sex steroid hormone receptors, tumor suppressor gene products (p53 and Rb), and cyclin E in uterine endometrioid carcinoma. Cancer. 1996 Jan 15;77(2):321–329. doi: 10.1002/(SICI)1097-0142(19960115)77:2<321::AID-CNCR15>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
- Linardopoulos S., Papadakis E., Delakas D., Theodosiou V., Cranidis A., Spandidos D. A. Human lung and bladder carcinoma tumors as compared to their adjacent normal tissue have elevated AP-1 activity associated with the retinoblastoma gene promoter. Anticancer Res. 1993 Jan-Feb;13(1):257–262. [PubMed] [Google Scholar]
- Mayol X., Garriga J., Graña X. G1 cyclin/CDK-independent phosphorylation and accumulation of p130 during the transition from G1 to G0 lead to its association with E2F-4. Oncogene. 1996 Jul 18;13(2):237–246. [PubMed] [Google Scholar]
- Mori A., Higashi H., Hoshikawa Y., Imamura M., Asaka M., Hatakeyama M. Granulocytic differentiation of myeloid progenitor cells by p130, the retinoblastoma tumor suppressor homologue. Oncogene. 1999 Nov 4;18(46):6209–6221. doi: 10.1038/sj.onc.1203044. [DOI] [PubMed] [Google Scholar]
- Mulligan G., Jacks T. The retinoblastoma gene family: cousins with overlapping interests. Trends Genet. 1998 Jun;14(6):223–229. doi: 10.1016/s0168-9525(98)01470-x. [DOI] [PubMed] [Google Scholar]
- Nishitani J., Nishinaka T., Cheng C. H., Rong W., Yokoyama K. K., Chiu R. Recruitment of the retinoblastoma protein to c-Jun enhances transcription activity mediated through the AP-1 binding site. J Biol Chem. 1999 Feb 26;274(9):5454–5461. doi: 10.1074/jbc.274.9.5454. [DOI] [PubMed] [Google Scholar]
- Pupa S. M., Howard C. M., Invernizzi A. M., De Vecchi R., Giani C., Claudio P. P., Colnaghi M. I., Giordano A., Ménard S. Ectopic expression of pRb2/p130 suppresses the tumorigenicity of the c-erbB-2-overexpressing SKOV3 tumor cell line. Oncogene. 1999 Jan 21;18(3):651–656. doi: 10.1038/sj.onc.1202363. [DOI] [PubMed] [Google Scholar]
- Schlott T., Reimer S., Jahns A., Ohlenbusch A., Ruschenburg I., Nagel H., Droese M. Point mutations and nucleotide insertions in the MDM2 zinc finger structure of human tumours. J Pathol. 1997 May;182(1):54–61. doi: 10.1002/(SICI)1096-9896(199705)182:1<54::AID-PATH815>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
- Susini T., Baldi F., Howard C. M., Baldi A., Taddei G., Massi D., Rapi S., Savino L., Massi G., Giordano A. Expression of the retinoblastoma-related gene Rb2/p130 correlates with clinical outcome in endometrial cancer. J Clin Oncol. 1998 Mar;16(3):1085–1093. doi: 10.1200/JCO.1998.16.3.1085. [DOI] [PubMed] [Google Scholar]
- Tanaka N., Odajima T., Nakano T., Kimijima Y., Yamada S., Ogi K., Kohama G. Immunohistochemical investigation of new suppressor oncogene p130 in oral squamous cell carcinoma. Oral Oncol. 1999 May;35(3):321–325. doi: 10.1016/s1368-8375(98)00089-x. [DOI] [PubMed] [Google Scholar]
- Tang Z., Treilleux I., Brown M. A transcriptional enhancer required for the differential expression of the human estrogen receptor in breast cancers. Mol Cell Biol. 1997 Mar;17(3):1274–1280. doi: 10.1128/mcb.17.3.1274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Udvadia A. J., Rogers K. T., Higgins P. D., Murata Y., Martin K. H., Humphrey P. A., Horowitz J. M. Sp-1 binds promoter elements regulated by the RB protein and Sp-1-mediated transcription is stimulated by RB coexpression. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3265–3269. doi: 10.1073/pnas.90.8.3265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weinberg R. A. The retinoblastoma protein and cell cycle control. Cell. 1995 May 5;81(3):323–330. doi: 10.1016/0092-8674(95)90385-2. [DOI] [PubMed] [Google Scholar]
- Yeung R. S., Bell D. W., Testa J. R., Mayol X., Baldi A., Graña X., Klinga-Levan K., Knudson A. G., Giordano A. The retinoblastoma-related gene, RB2, maps to human chromosome 16q12 and rat chromosome 19. Oncogene. 1993 Dec;8(12):3465–3468. [PubMed] [Google Scholar]