The P53 homolog p63 encodes multiple proteins with transactivating, apoptosis-inducing, and oncogenic activities. We showed that p63 is amplified and that DeltaNp63 isotypes are overexpressed in squamous cell carcinoma (SCC) and enhance oncogenic growth in vitro and in vivo. Moreover, p53 associated with DeltaNp63alpha and mediated its degradation. Here, we report that DeltaNp63 associates with the B56alpha regulatory subunit of protein phosphatase 2A (PP2A) and glycogen synthase kinase 3beta (GSK3beta), leading to a dramatic inhibition of PP2A-mediated GSK3beta reactivation. The inhibitory effect of DeltaNp63 on GSK3beta mediates a decrease in phosphorylation levels of beta-catenin, which induces intranuclear accumulation of beta-catenin and activates beta-catenin-dependent transcription. Our results suggest that DeltaNp63 isotypes act as positive regulators of the beta-catenin signaling pathway, providing a basis for their oncogenic properties.

No abstract

No abstract

Dear Sir,The involvement of the mouse mammary tumor virus (MMTV) in breast cancer has long been postulated but never proven. Two studies have detected the sequence of the MMTV env gene in more than one-third of breast tumor tissues. 1,2 The present study was designed to investigate whether this viral sequence could serve as a molecular marker for the detection of breast cancer. We amplified the viral sequence in 2 cell lines and 18 breast tumor samples, using PCR, PCR Southern hybridization and real-time PCR. Surprisingly, we could not detect the viral sequence in any of these samples despite amplification in positive controls. Our study calls into question the role of MMTV in human breast cancer tumorigenesis.The involvement of retroviruses in human cancer was established long ago, e.g., HPV in cervical and oropharyngeal tumors. 3,4 The participation of a virus similar to MMTV in human breast cancer has long been postulated but never demonstrated. Several lines of evidence suggested the involvement of MMTV-like retroviruses in human breast cancer. Previously, it was shown that MMTV is an agent associated with a high incidence of breast cancer in mice. 5 Detectable MMTV env gene-related antigenic reactivity was found in tissue sections of breast cancer, 6 -10 breast cancer cell lines, 11 serum, 12,13 pleural effusion 14 and lymph nodes. 15 Moreover, sequence homology to MMTV has been found in human DNA. 1,2,16 -21 Two studies detected the env gene of MMTV in 37-38.5% of breast tumor tissues but only in 0 -2% of normal tissues. 1,2 According to these studies, this viral sequence was highly specific to breast tumor tissues and was not detected in other tumor tissues.The present study was designed to examine whether the env gene of MMTV could be used as a molecular marker for the detection of breast cancer. We planned to evaluate, by real-time PCR, a panel of normal tissues, tumor breast tissues and blood samples from 40 breast cancer patients. MMTV env gene plasmid and MCF-7 and MB-MDA-231 cell lines were used as a positive control, as described in previous studies. 1,2,11,17 The viral sequence was first amplified by regular PCR; then, PCR products were hybridized with an internal probe by PCR Southern hybridization; finally, real-time PCR was performed. We were unable to detect the viral sequence in the cell lines or in the breast tumor tissues despite robust amplification from the plasmid control. MATERIAL AND METHODS Cell lines and tumor tissuesThe MCF-7 and MB-MDA-231 cell lines were purchased from the ATCC (Manassas, VA) and grown in RPMI medium with FBS 10%, penicillin and streptomycin 1%.Eighteen invasive ductal carcinomas of the breast from 17 patients were collected at the