Item Infomation
| Title: | The role of ATF-3 in physiologic and neoplastic cellular proliferation |
| Authors: | Woo , Sook-bin Sroussi , Herve Y. Menon , Reshma Mitchell, Richard N. |
| Description: | Activating transcription factor 3 (ATF-3), a cyclic AMP-dependent transcription factor that is encoded by the ATF-3 gene, plays a potential regulatory role in physiologic and pathologic cell proliferation including wound healing and cancer. However, data is limited that compares and contrasts its mechanistic role in the regulation of regenerative cell proliferation in healing responses seen in oral mucosal reparative cell proliferation or scar formation affecting traumatized skin, and in the unregulated cell behavior as exemplified in the standard cancer progression models such as human melanoma. To this end, we evaluated ATF-3 expression during re-epithelialization at wound edges in oral mucosa and skin as well in a more in-depth mechanistic manner in the context of melanoma progression models. We found no significant differences by immunofluorescence microscopy in ATF-3 immunoreactivity between wound edges of ulcerated human skin and oral tissue types as they both exhibited similarly increased ATF-3 expression in comparison to its normal counterparts. In contrast, ATF-3 staining declined in metastatic versus primary melanoma cell lines and with progression from patient nevi to primary to metastatic melanomas. Analysis of TCGA melanoma database exhibited lower ATF-3 expression which correlated with poor prognosis. Metastatic melanoma cell lines with retrovirally-induced ATF-3 overexpression (A2058 and C8161 ATF-3 OE) exhibited decreased proliferation, migration and invasion in vitro. GO and KEGG analyses of the RNA seq data showed downregulation of phosphorylated ERK and AKT in A2058 ATF-3 OE cells that was further validated by Western Blot. In vivo, xenografted A2058 ATF-3 OE cells formed smaller and less abundant tumors in murine subcutis than did control cells, and Ki-67 staining confirmed lower labeling indices in ATF-3 overexpressing lesions. Taken collectively, ATF-3 appears to play a dichotomous role in reparative versus neoplastic cell proliferations, with increased expression associated with the former and decreased expression with the latter. Aside from its potential use as a biomarker to define cell subpopulations most actively involved in tissue repair, it also may serve as a target for novel therapeutic approaches to inhibiting the virulence of cancers that affect skin and oral mucosa. |
| URI: | http://lib.yhn.edu.vn/handle/YHN/157 |
| Other Identifiers: | Wang , Diana. 2021. The role of ATF-3 in physiologic and neoplastic cellular proliferation. Doctoral dissertation, Harvard University School of Dental Medicine. 28498203 https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37369026 0000-0002-5474-7287 |
| Appears in Collections | Y học |
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