p21 WAF1/CIP1 is a Downstream target of ELK-1 Growth / Tumor Suppressor Pathway in Breast and Androgenindependent Prostate Cancers Volume 4 - Issue 5

Jingyao Xu¹, Zerak Kabir¹, Kartik Aysola¹, Yuli Chai¹, Nina Wyatt¹, Shai Waldrip¹, Alexis Clark¹, Michelle Lee², Vaishali Reddy², Manan Shah², Eric Chang², Joe^l Okoli³, E Shyam P Reddy¹ and Veena N Rao¹*

• ¹Department of Neurology, Foshan Hospital of Traditional Chinese Medicine, China
• ²Department of Biochemistry and Molecular Biology, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, China
• ³Department of Neurology, Guangdong Province Hospital of Traditional Chinese Medicine, China
• ⁴Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, China

Received:June 01, 2021   Published: July 30, 2021

Corresponding author: Veena N Rao, Professor and Co-Director Cancer Biology Program, GCC Distinguished Cancer Scholar, Department of OB/GYN, Morehouse School of Medicine, RW D-335, 720 Westview Drive, Atlanta, Georgia 30303-3031. Phone 404- 756-5755, Fax 404-756-8828

DOI: 10.32474/OAJOM.2021.04.000197

 

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Abstract

African American men have the highest risk of developing prostate cancer and have more than twice the mortality rate compared to Caucasian men in the US. ELK-1 belongs to the ETS family of ternary complex factors that plays a major role in cell proliferation, tumorigenesis, as well as differentiation. We have previously shown ELK-1 to not only suppress growth but also to augment the growth suppressive function of BRCA1 proteins in human breast cancer cells. In the current study we have demonstrated for the first time Elk-1 to inhibit the growth of androgen-independent prostate cancer cells. ELK-1 transfected prostate and breast cancer cells were slow growing and inhibited in their capacity to form colonies in soft agar. The p21WAF1/CIP1 protein was found to be expressed at elevated levels both in ELK-1 transfected breast and prostate cancer cells. The p21WAF1/CIP1 promoter activity was also enhanced in the presence of increasing concentrations of ELK-1 protein. Furthermore, ELK-1 protein by binding to the ETS binding motif in the p21WAF1/CIP1 promoter induced the expression of the protein in a p53-independent manner. This work suggests for the first time ELK-1 to function as a growth /tumor suppressor of androgen independent human prostate and breast cancer cells by activating p21WAF1/CIP1 independent of the presence of p53. These findings can provide a novel mechanism that can bypass the p53 defect in tumors with endogenous p53 mutations thus developing effective therapy for patients with advancedstage androgen independent prostate and breast cancers.

Keywords: Elk-1, Breast cancer, Androgen Receptor, Androgen-independent Prostate Cancer, Growth / Tumor Suppressor, p21 WAF1/CIP1

Abbreviations: ELK-1: ETS like gene; AIPC: Androgen-independent prostate cancer; AR: Androgen Receptor; AA: African American; TCF: ternary complex factors; CRPC: Castration resistant prostate cancers; SRE: serum response element; SRF: Serum response factor.

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