Expression of Androgen Receptor Is Negatively Regulated By p53
Increased expression of androgen receptor (AR) in prostate cancer (PC) is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2007-12-01
|
| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558607801254 |
| _version_ | 1828395253030191104 |
|---|---|
| author | Fatouma Alimirah Ravichandran Panchanathan Jianming Chen Xiang Zhang Shuk-Mei Ho Divaker Choubey |
| author_facet | Fatouma Alimirah Ravichandran Panchanathan Jianming Chen Xiang Zhang Shuk-Mei Ho Divaker Choubey |
| author_sort | Fatouma Alimirah |
| collection | DOAJ |
| description | Increased expression of androgen receptor (AR) in prostate cancer (PC) is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs). We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic stress or by inhibition of p53 nuclear export downregulated the expression of AR. Furthermore, forced expression of p53 in LNCaP cells decreased the expression of AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR expression. Consistent with the negative regulation of AR expression by p53, the p53-null HCT116 cells expressed higher levels of AR compared with the isogenic HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide treated LNCaP cells p53 bound to the promoter region of the AR gene, which contains a potential p53 DNA-binding consensus sequence, in chromatin immunoprecipitation assays. Together, our observations provide support for the idea that the loss of p53 function in prostate cancer cells contributes to increased expression of AR. |
| first_indexed | 2024-12-10T08:09:35Z |
| format | Article |
| id | doaj.art-03dcc581a46d4d2b9d7483feee4fd519 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-10T08:09:35Z |
| publishDate | 2007-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-03dcc581a46d4d2b9d7483feee4fd5192022-12-22T01:56:36ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022007-12-019121152115910.1593/neo.07769Expression of Androgen Receptor Is Negatively Regulated By p53Fatouma Alimirah0Ravichandran Panchanathan1Jianming Chen2Xiang Zhang3Shuk-Mei Ho4Divaker Choubey5Edward Hines Jr. VA Hospital, Hines, IL 60141, USALoyola University Chicago, Maywood, IL 60153, USALoyola University Chicago, Maywood, IL 60153, USADepartment of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267, USADepartment of Environmental Health, University of Cincinnati, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH 45267, USAEdward Hines Jr. VA Hospital, Hines, IL 60141, USAIncreased expression of androgen receptor (AR) in prostate cancer (PC) is associated with transition to androgen independence. Because the progression of PC to advanced stages is often associated with the loss of p53 function, we tested whether the p53 could regulate the expression of AR gene. Here we report that p53 negatively regulates the expression of AR in prostate epithelial cells (PrECs). We found that in LNCaP human prostate cancer cells that express the wild-type p53 and AR and in human normal PrECs, the activation of p53 by genotoxic stress or by inhibition of p53 nuclear export downregulated the expression of AR. Furthermore, forced expression of p53 in LNCaP cells decreased the expression of AR. Conversely, knockdown of p53 expression in LNCaP cells increased the AR expression. Consistent with the negative regulation of AR expression by p53, the p53-null HCT116 cells expressed higher levels of AR compared with the isogenic HCT116 cells that express the wildtype p53. Moreover, we noted that in etoposide treated LNCaP cells p53 bound to the promoter region of the AR gene, which contains a potential p53 DNA-binding consensus sequence, in chromatin immunoprecipitation assays. Together, our observations provide support for the idea that the loss of p53 function in prostate cancer cells contributes to increased expression of AR.http://www.sciencedirect.com/science/article/pii/S1476558607801254Prostate cancerandrogen receptorp53DNA damagetranscriptional repression |
| spellingShingle | Fatouma Alimirah Ravichandran Panchanathan Jianming Chen Xiang Zhang Shuk-Mei Ho Divaker Choubey Expression of Androgen Receptor Is Negatively Regulated By p53 Neoplasia: An International Journal for Oncology Research Prostate cancer androgen receptor p53 DNA damage transcriptional repression |
| title | Expression of Androgen Receptor Is Negatively Regulated By p53 |
| title_full | Expression of Androgen Receptor Is Negatively Regulated By p53 |
| title_fullStr | Expression of Androgen Receptor Is Negatively Regulated By p53 |
| title_full_unstemmed | Expression of Androgen Receptor Is Negatively Regulated By p53 |
| title_short | Expression of Androgen Receptor Is Negatively Regulated By p53 |
| title_sort | expression of androgen receptor is negatively regulated by p53 |
| topic | Prostate cancer androgen receptor p53 DNA damage transcriptional repression |
| url | http://www.sciencedirect.com/science/article/pii/S1476558607801254 |
| work_keys_str_mv | AT fatoumaalimirah expressionofandrogenreceptorisnegativelyregulatedbyp53 AT ravichandranpanchanathan expressionofandrogenreceptorisnegativelyregulatedbyp53 AT jianmingchen expressionofandrogenreceptorisnegativelyregulatedbyp53 AT xiangzhang expressionofandrogenreceptorisnegativelyregulatedbyp53 AT shukmeiho expressionofandrogenreceptorisnegativelyregulatedbyp53 AT divakerchoubey expressionofandrogenreceptorisnegativelyregulatedbyp53 |