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. 2004 Dec 15:4:91.
doi: 10.1186/1471-2407-4-91.

Wnt1 is epistatic to Id2 in inducing mammary hyperplasia, ductal side-branching, and tumors in the mouse

Susan Marino  1 , Claire Romelfanger, Yoshifumi Yokota, Roel Nusse
Affiliations

Wnt1 is epistatic to Id2 in inducing mammary hyperplasia, ductal side-branching, and tumors in the mouse

Susan Marino et al. BMC Cancer. .

Abstract

Background: During pregnancy, the mammary glands from Id2 mutant animals are deficient in lobulo-alveolar development. This failure of development is believed to be due to a proliferation defect.

Methods: We have asked whether functional Id2 expression is necessary for Wnt induced mammary hyperplasia, side branching, and cancer, by generating mice expressing a Wnt1 transgene in an Id2 mutant background.

Results: We show in this work that forced expression of Wnt1 in the mammary gland is capable of overcoming the block to proliferation caused by the absence of Id2. We also show that Wnt1 expression is able to cause mammary tumors in an Id2 mutant background.

Conclusions: We conclude that functional Id2 expression is not required for Wnt1 to induce mammary hyperplasia and mammary tumors.

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Figures

Figure 1
Figure 1
The Wnt1 transgene was crossed into an Id2 -/- background in order to produce cohorts of WT, Id2 +/-, and Id2 -/- females with and without the Wnt1 transgene. The scheme was designed so that mothers could feed their own young and so that all cohorts being compared would share a common background.
Figure 2
Figure 2
Carmine stained mammary gland whole mounts were made from virgin females. Top row, left to right: normal mammary gland development was observed in wild type (13 weeks), Id2 +/- (26 weeks), and Id2-/- (26 weeks) animals. Bottom row, left to right: Wnt1 induced hyperplasia and side branching were forced when the MMTV-Wnt1 transgene was present in wild type, Id2+/-, and Id2 -/- animals (all 19 weeks). Branching patterns are representative of a consistent phenotype observed in all mice and in both tumor-free glands and in glandular tissue associated with tumors in the MMTV-Wnt1 mice.
Figure 3
Figure 3
Three cohorts of mice, MMTV-Wnt1 Tg (n = 21), MMTV-Wnt1 Tg; Id2 +/- (n = 23), and MMTV-Wnt1 Tg; Id2 -/- (n = 8) were examined weekly by visual examination and palpation. No differences in tumor incidence were observed. MMTV-Wnt1 Tg : square; MMTV-Wnt1 Tg; Id2 +/- : diamond; MMTV-Wnt1 Tg; Id2 -/-: triangle.
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