Abstract:
:The inactivation of certain tumor suppressor genes is thought to play an important role in the genesis of a number of tumor types. For example, inactivation of the Retinoblastoma (Rb) tumor suppressor is frequently observed in a proportion of sporadic human breast cancers. While these studies suggest that inactivation of key tumor suppressor genes may play an important role in the induction of mammary cancers, direct evidence supporting this contention is lacking. Because polyomavirus (PyV) Large T (LT) antigen is known to associate with and inactivate certain members of the Rb family (p105Rb, p107, p130), we have derived transgenic mice which express PyV LT antigen in the mammary epithelium. As expected mammary epithelial-specific expression of PyV LT antigen resulted in the induction of mammary tumors which correlated with their capacity to associate with Rb family members. In addition to mammary carcinomas, female transgenic mice expressing the PyV LT transgene frequently develop uterine leiomyomas. Because loss of heterozygosity involving the human CUTL1 (Cut like 1) gene located at chromosomal position 7q22 has been recently implicated in sporadic human uterine leiomyomas, we tested the hypothesis that PyV LT antigen may also form specific complexes with CUTL1. The results of these analyses revealed that specific complexes of CUTL1 and PyV LT antigen could be detected in both leiomyomas and mammary tumors. Taken together, these observations suggest that PyV LT antigen may be involved in inducing these tumors by sequestering both CUTL1 and Rb growth regulatory proteins.
journal_name
Oncogenejournal_title
Oncogeneauthors
Webster MA,Martin-Soudant N,Nepveu A,Cardiff RD,Muller WJdoi
10.1038/sj.onc.1201707subject
Has Abstractpub_date
1998-04-16 00:00:00pages
1963-72issue
15eissn
0950-9232issn
1476-5594journal_volume
16pub_type
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