Year: 2012
Type: dissertation
Abstract: \ny-synuclein is the third and last discovered member of the synuclein family, it is expressed mostly in the nervous system and its physiological function is still unknown. y-synuclein has been claimed to play a role in mammary gland tumourigenesis as its overexpression in cancer cells was shown to inhibit apoptosis and stimulate growth, proliferation, survival, motility and metastasis. However, the role of endogenous y-synuclein in mammary gland tumourigenesis has not been studied in an appropriate in vivo model. The results obtained in this study show that y-synuclein is not required for the normal development of the mammary gland at any developmental stage - embryonic, pubertal or reproductive. Furthermore, ablation of y-synuclein did not prevent induction of mammary gland tumours by activated ErbB2 transgene in mammary gland epithelium. Unexpectedly, transgenic activated ErbB2 hemizygous, y-synuclein knockout female mice developed slightly more tumours with a significantly shorter tumour latency than the wild type littermates. These animals also exhibited similar tumour growth rates and metastases to the lungs, and a slightly shorter survival. Overall, a trend for accelerated tumourigenesis in the absence of y-synuclein was observed. Thus, it is feasible that the aberrant expression of y-synuclein reported in advance-stage tumours and metastases reflects activation of pathways aimed at repressing rather than enhancing tumourigenesis, as widely thought. Future studies will clarify the role of y-synuclein in ErbB2-induced mammary gland tumourigenesis.
Author: Essam Sharfeddin
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2123065271