Discipline of Surgical Specialties, Adelaide Medical School, The Queen Elizabeth Hospital, University of Adelaide, Woodville, SA 5011, Australia; and Robinson Research Institute, University of Adelaide, SA 5005, Australia.
Discipline of Surgical Specialties, Adelaide Medical School, The Queen Elizabeth Hospital, University of Adelaide, Woodville, SA 5011, Australia.
Reprod Fertil Dev. 2020 May;32(8):774-782. doi: 10.1071/RD19378.
Female mice heterozygous for a genetic mutation in transcription factor forkhead box p3 (Foxp3) spontaneously develop mammary cancers; however, the underlying mechanism is not well understood. We hypothesised that increased cancer susceptibility is associated with an underlying perturbation in mammary gland development. The role of Foxp3 in mammary ductal morphogenesis was investigated in heterozygous Foxp3Sf/+ and wildtype Foxp3+/+ mice during puberty and at specific stages of the oestrous cycle. No differences in mammary ductal branching morphogenesis, terminal end bud formation or ductal elongation were observed in pubertal Foxp3Sf/+ mice compared with Foxp3+/+ mice. During adulthood, all mice underwent normal regular oestrous cycles. No differences in epithelial branching morphology were detected in mammary glands from mice at the oestrus, metoestrus, dioestrus and pro-oestrus stages of the cycle. Furthermore, abundance of Foxp3 mRNA and protein in the mammary gland and lymph nodes was not altered in Foxp3Sf/+ mice compared with Foxp3+/+ mice. These studies suggest that Foxp3 heterozygosity does not overtly affect mammary gland development during puberty or the oestrous cycle. Further studies are required to dissect the underlying mechanisms of increased mammary cancer susceptibility in Foxp3Sf/+ heterozygous mice and the function of this transcription factor in normal mammary gland development.
杂合转录因子叉头框 P3（Foxp3）基因突变的雌性小鼠自发发生乳腺癌；然而，其潜在机制尚不清楚。我们假设，癌症易感性的增加与乳腺发育的潜在扰动有关。在青春期和发情周期的特定阶段，研究了杂合 Foxp3Sf/+和野生型 Foxp3+/+小鼠中 Foxp3 在乳腺导管形态发生中的作用。与 Foxp3+/+小鼠相比，Foxp3Sf/+小鼠在青春期的乳腺导管分支形态发生、终末芽形成或导管伸长方面没有差异。在成年期，所有小鼠都经历了正常的定期发情周期。在发情、间情期、动情前期和动情后期的发情周期中，乳腺中的上皮分支形态没有差异。此外，Foxp3Sf/+小鼠乳腺和淋巴结中 Foxp3 mRNA 和蛋白的丰度与 Foxp3+/+小鼠没有差异。这些研究表明，Foxp3 杂合性在青春期或发情周期不会明显影响乳腺发育。需要进一步研究来剖析 Foxp3Sf/+杂合小鼠中增加的乳腺癌易感性的潜在机制以及该转录因子在正常乳腺发育中的功能。
