Left-Right Asymmetry in Embryonic Development and Breast Cancer: Common Molecular Determinants?

J.      Wilting; M.      Hagedorn

doi:10.2174/092986711798347252

Abstract

At the first glance the vertebrate body appears to be symmetric, however, left and right sides are different. This is tightly controlled during embryonic development, and may as well affect the spatial occurrence of diseases. In the embryo, determination of the left and right sides takes place before and during gastrulation. Its failure results in heterotaxia, a diverse group of congenital laterality disorders characterized by left-right displacement of organs. In recent years, our knowledge about the molecular control of left-right asymmetry during embryonic development has grown considerably. However, almost nothing is known about the etiology of cancer laterality. Mammary carcinoma is 5 - 10% more likely to arise in the left breast. The left side of the body is also 10% more prone to melanoma development. Whereas the right predominance of lung, ovarian and testicular cancer might be explained by the greater organ mass on that side, possible reasons for left predominance of mammary carcinoma and melanoma are highly speculative. Sleeping behavior, handedness, nursing behavior and asymmetric sun exposure were named. A possible interrelation between the molecular control of left-right asymmetry and cancer has not yet been discussed in detail. Here we present an overview of molecules involved in both processes, focusing on laterality of breast cancer. Several secreted and membrane-bound growth factors such as Nodal, Lefty, FGF, HB-EGF and HGF as well as transcription factors (e.g. Pitx2, FoxA2) may be candidates with such overlapping functions. Studies on cancer laterality in transgenic mice are needed to make progress in this neglected research field.

Keywords: Laterality, Left-right asymmetry, Breast cancer, Notch, Nodal, Lefty, Pitx2, FGF, HB-EGF, HGF, FoxA2