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Series GSE7135 Query DataSets for GSE7135
Status Public on Dec 31, 2007
Title Mutant p53 Increases Incidence and Promotes Progression of Mammary Carcinomas in Mice
Organism Mus musculus
Experiment type Genome variation profiling by array
Summary In human breast cancer, mutations in the p53 gene are associated with poor prognosis, suggesting a mutant p53 “gain of function”. To study this phenomenon, we co-expressed mutant p53R270H in mice in which SV40 early proteins initiate the development of mammary adenocarcinomas in descendants of mammary epithelial cells that survived involution (WAPT-mice). This model allows the characterization of mammary carcinomas that developed in the absence or presence of mutant p53, while the endogenous wild-type p53 is functionallycompromised. Co-expression of mutant p53 significantly aggravated the phenotype of bitransgenic mice, as evidenced by a higher tumor incidence, a worse clinical staging and histological grading, as well as an enhanced invasiveness of the tumors, and more frequent pulmonary metastasis. Our data indicate that mutant p53 does not exert this effect by increasing genomic instability. On the contrary, lower grade tumors in WAP-T mice generally accumulated more amplifications of pro-survival genes than the corresponding tumors in bitransgenic animals, suggesting that mutant p53 can compensate for such genetic alterations by alternative mechanisms, possibly by its transcriptional activities, and thereby facilitate tumor formation. As a common feature and associated with their enhanced invasiveness, high grade tumors showed high level amplification of the Met-locus.
Keywords: mutant p53, SV40 early proteins, tumor progression, tumor grade, tumor stage, mammary carcinoma, animal model, Met
Overall design Analysis of 34 mammary carcinomas of different histological grades derived from WAP-T and WAP-T x WAP-mutp53 transgenic mice.
Contributor(s) Heinlein C, Krepulat F, Löhler J, Ylstra B, Krugers T, Tolstonog GV, Deppert W
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Submission date Feb 26, 2007
Last update date Mar 16, 2012
Contact name Daoud Sie
Phone +31 20 4442428
Organization name Vrije Universiteit Medical Center
Department Pathology
Lab Microarray Core Facility
Street address De Boelelaan 1117
City Amsterdam
ZIP/Postal code 1081 HV
Country Netherlands
Platforms (1)
GPL4468 VUMC MACF Mouse 38K oligo v64
Samples (38)
GSM149405 Grade 2 (10864-6_vs_11155-9_s34_b64_MACF_Influence of mutp53 on progression of mammary adenocarcinoma )
GSM149406 Grade 1 (10681-7_vs_10699-9_s57_b64_MACF_Influence of mutp53 on progression of mammary adenocarcinoma)
GSM149407 Grade 3 (10680-7_vs_10699-9_s66_b64_MACF_Influence of mutp53 on progression of mammary adenocarcinoma)
BioProject PRJNA98203

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