High-mobility group (HMG) A1
proteins including HMGA1a and HMGA1b are chromosomal
proteins that function in a variety of cellular processes such as cell growth, transcription regulation, neoplastic transformation, and progression. Overexpression of HMGA1
proteins has been associated with almost every type of
cancer cells. Post-translational modifications (PTMs) of HMGA1
proteins in different types of human
cancer cell lines have been extensively explored over the past decade. Here, we extended the identification of PTMs of HMGA1
proteins to human
breast tumor tissue specimens with different
carcinoma progression stages (metastatic and primary
cancer) as well as the paired adjacent normal breast tissues. In this regard, we employed tandem mass spectrometry to examine the nature and sites of PTMs of HMGA1
proteins isolated from cancerous/normal human breast tissues. Novel PTMs of
HMGA1a protein, that is, monomethylation at Lys30 and Lys54 as well as monophosphorylation at Ser43 and Ser48, were detected in
cancer tissues. In these
cancer tissues, we also found C-terminal constitutive phosphorylation in HMGA1a and HMGA1b as well as mono- and dimethylation of Arg25 in HMGA1a, which were previously found to be present in these
proteins isolated from human
cancer cell lines. Furthermore, a more complex spectrum of PTMs on HMGA1
proteins was correlated with a more aggressive
malignancy in human
breast cancer tissues.