Klinowska T C, Alexander C M, Georges-Labouesse E, Van der Neut R, Kreidberg J A, Jones C J, Sonnenberg A, Streuli C H
School of Biological Sciences, University of Manchester, 3.239 Stopford Building, Oxford Road, Manchester, M13 9PT, United Kingdom.
Dev Biol. 2001 May 15;233(2):449-67. doi: 10.1006/dbio.2001.0204.
In the mammary gland, both laminin and integrins have been shown to be required for normal ductal morphogenesis during development in vivo, and for functional differentiation in culture models. Major integrin receptors for laminins in the mammary gland are alpha 3 beta 1, alpha 6 beta 1, and alpha 6 beta 4. However, the specific subunits that contribute to laminin-mediated mammary cell function and development have not been identified. In this study, we use a genetic approach to test the hypothesis that laminin-binding integrins are required for the function of the mammary gland in vivo. Rudiments of embryonic mammary gland were shown to develop in the absence of these integrin subunits. Postnatal development of the mammary gland was studied in integrin null tissue that had been transplanted into the mammary fat pads of syngeneic hosts. In mammary epithelium lacking alpha 6 integrin, the beta 4 subunit was not apparent and hemidesmosome formation was only rudimentary. However, despite this deficiency, normal ductal morphogenesis and branching of the mammary gland occurred and myoepithelial cells were distributed normally with respect to luminal cells. Mammary alveoli devoid of alpha 3 or alpha 6 integrin formed in pregnancy and were histologically and functionally identical to those in wild-type mammary gland. The tissue underwent full morphological differentiation, and the epithelial cells retained the ability to synthesize beta-casein. This work demonstrates that mammary tissue genetically lacking major laminin-binding integrin receptors is still able to develop and function.
在乳腺中，层粘连蛋白和整合素均已被证明是体内发育过程中正常导管形态发生以及培养模型中功能分化所必需的。乳腺中层粘连蛋白的主要整合素受体是α3β1、α6β1和α6β4。然而，尚未确定对层粘连蛋白介导的乳腺细胞功能和发育有贡献的特定亚基。在本研究中，我们采用遗传学方法来检验层粘连蛋白结合整合素是体内乳腺功能所必需的这一假设。结果表明，在没有这些整合素亚基的情况下，胚胎乳腺原基仍能发育。我们对已移植到同基因宿主乳腺脂肪垫中的整合素缺失组织进行了乳腺出生后发育的研究。在缺乏α6整合素的乳腺上皮中，β4亚基不明显，半桥粒的形成也仅处于初级阶段。然而，尽管存在这种缺陷，乳腺仍发生了正常的导管形态发生和分支，肌上皮细胞相对于管腔细胞的分布也正常。在妊娠期间形成了缺乏α3或α6整合素的乳腺腺泡，其在组织学和功能上与野生型乳腺中的腺泡相同。该组织经历了完全的形态分化，上皮细胞保留了合成β-酪蛋白的能力。这项工作表明，在基因上缺乏主要层粘连蛋白结合整合素受体的乳腺组织仍然能够发育并发挥功能。
