HOXB1Mutations Disrupt MEIS1-HOXB13 Mediated Tumor Suppression
Session Number
MEDH 52
Advisor(s)
Mathias Morales, Ryan Brown, Donald Vander Griend, University of Illinois Chicago, Department of Pathology
Discipline
Medical and Health Sciences
Start Date
17-4-2025 10:45 AM
End Date
17-4-2025 11:00 AM
Abstract
Prostate cancer is the second most common cancer in men and ranks sixth in cancer-related mortalities. One avenue of research aims to demonstrate how mutations in the more clinically mutated HOXB13 affect MEIS1’s impact in regulating proteoglycans decorin and lumican in castration resistant prostate cancer. The lab has already demonstrated MEIS1-HOXB13’s role in impacting decorin and lumican; however, it is still unknown how mutations in HOXB13 can play a role in advanced disease. Thus, this research aimed to elucidate how these mutations impact tumor suppression. Prostate cancer cell lines, 22Rv1 and LAPC4, were modulated to either overexpress MEIS1 or have B13 knocked out of the genome. The cell lines were then infected with replacement HOXB13 genes with mutations of interest: G84E, Y88D, L144P, and X285K. Western blots and qPCRs were done to quantify decorin and lumican in both the in vivo samples and cell lines. It was found that mutated HOXB13 impacted MEIS1’s ability to regulate decorin and lumican levels at the transcription and protein level compared to control. This finding in vivo and in vitro was supported by an increase in tumor growth and cell line growth, demonstrating the mutation’s clinical relevance.
HOXB1Mutations Disrupt MEIS1-HOXB13 Mediated Tumor Suppression
Prostate cancer is the second most common cancer in men and ranks sixth in cancer-related mortalities. One avenue of research aims to demonstrate how mutations in the more clinically mutated HOXB13 affect MEIS1’s impact in regulating proteoglycans decorin and lumican in castration resistant prostate cancer. The lab has already demonstrated MEIS1-HOXB13’s role in impacting decorin and lumican; however, it is still unknown how mutations in HOXB13 can play a role in advanced disease. Thus, this research aimed to elucidate how these mutations impact tumor suppression. Prostate cancer cell lines, 22Rv1 and LAPC4, were modulated to either overexpress MEIS1 or have B13 knocked out of the genome. The cell lines were then infected with replacement HOXB13 genes with mutations of interest: G84E, Y88D, L144P, and X285K. Western blots and qPCRs were done to quantify decorin and lumican in both the in vivo samples and cell lines. It was found that mutated HOXB13 impacted MEIS1’s ability to regulate decorin and lumican levels at the transcription and protein level compared to control. This finding in vivo and in vitro was supported by an increase in tumor growth and cell line growth, demonstrating the mutation’s clinical relevance.