NucleaRDB: Extraction of mutation data from the literature

2005, NucleaRDB.

This data was extracted from Medline abstracts and full texts (when available) in an automated manner.

The table below describes the selected point mutation and provides links to other documents. The sentence(s) where the point mutation P151S was found are listed after the table.

The mutated residues are also indicated in the family sequence alignments and hyperlinked to the corresponding mutation pages.

Point mutation P151S in ANDR_HUMAN

Point mutation:	P151S
Domain:	N-term
General numbering (NucleaRDB):	-
Protein:	ANDR_HUMAN (AR,DHTR, NR3C)	Swiss-Prot Cross-reference table Family page
Other point mutations / same protein	List of mutations in ANDR_HUMAN
Family alignments	3C4 Androgen (AR) 3C Glucocorticoid-like (GR,MR,PR,AR) 3 Estrogen like (ER,ERR,GR,MR,PR,AR)
Other point mutations / same position
Reference:	Androgen-independent growth of LNCaP prostate cancer cells is mediated by gain-of-function mutant p53. Nesslinger NJ, Shi XB, deVere White RW Cancer Res 2003 May 1;63(9):2228-33.	Medline
Other point mutations / same article	List
Text source	HTML full text
Validation status	Not yet checked

Relevant sentences:

P151S

We established five stably transfected LNCaP cell lines: four containing gain-of-function (GOF) mutant p53 alleles (G245S , R248W , R273H , and R273C) and one containing a non-GOF p53 mutant allele (P151S)
To study whether these GOF p53 mutants mediate progression of CaP to androgen independence , we selected four GOF alleles (G245S , R248W , R273H , and R273C) , which are frequent in CaP (15) , and a non-GOF mutant allele (P151S)
We found that the LNCaP cells transfected with each of four GOF mutant alleles were able to grow in the absence of androgens , whereas the non-GOF P151S-transfected LNCaP cells and the LNCaP parental cells could not , indicating that GOF p53 mutations can lead to AI growth of LNCaP cells
The G245S , R248W , R273H , R273C , and P151S alleles were individually cloned into the pCR 3.1 vector (Invitrogen , Carlsbad , CA) downstream of the cytomegalovirus promoter
Four GOF p53 mutant alleles (G245S , R248W , R273H , and R273C) and the non-GOF P151S mutant allele were selected for the present study
All are dominant negative , with the R248W , R273H , and R273C mutants dominant over two wt copies of p53 , and the G245S and P151S alleles dominant over one wt copy of p53
The LNCaP parental cells , the vector-only subline , the P151S subline , and the four GOF p53 sublines were grown for 5 days in androgen-depleted medium
The parental LNCaP cells and the P151S subline underwent a growth arrest (Fig. 2A)(image)
As shown in Fig. 2B(image) , the three control lines (the parental LNCaP , vector-only subline , and the P151S subline) failed to grow in androgen-depleted medium , whereas the four GOF p53 sublines were able to proliferate in the medium with a doubling-time of ~2.5 days for three of the sublines
Growth arrest was seen for the LNCaP cells and the non-GOF P151S subline (LNCaP+P151S) in androgen-depleted medium
B , the growth curves show that the four GOF p53 sublines continued to proliferate in androgen-depleted medium , whereas the LNCaP parental , vector-only , and P151S sublines do not proliferate in this medium
The LNCaP parental and P151S subline are used as controls , and have a large fold increase , reflecting the growth arrest of these cells in androgen-depleted medium
When these lines were grown in androgen-depleted medium , a slight decrease in the AR levels was observed in the parental , vector-only , and P151S lines
Consistent with AR expression levels , both the LNCaP parental cells and the P151S cells expressed high levels of PSA protein in androgen-containing medium , whereas the PSA levels were markedly decreased in androgen-depleted medium (Fig. 4A)(image)
There is no change in AR expression in the LNCaP parental , vector-only , and P151S sublines grown in androgen-containing medium or slight AR reduction in androgen-depleted medium
The LNCaP parental and P151S subline grown in androgen-containing medium produce high levels of PSA , whereas the four GOF p53 sublines have lower levels of PSA
On androgen depletion , PSA levels were much lower in the LNCaP parental and P151S cells , with levels undetectable in the four GOF mutant p53 sublines
Expression of PSA was highest in the LNCaP parental and P151S subline , whereas very little PSA expression was seen in the four GOF mutant p53 sublines
Bcl-2 expression increased in G245S , R248W , R273H , and P151S sublines in the presence of androgen , and their expression decreased after androgen withdrawal
As shown in Fig. 5(image) , transfection of the mutant p53 alleles into LNCaP cells resulted in increased Bcl-2 expression in the G245S , R248W , R273H , and P151S sublines when grown in androgen-containing medium , as compared with the parental and vector-only cells
Among these five mutants , only the four GOF p53 mutant sublines were able to grow in androgen-depleted medium , whereas the non-GOF P151S subline was unable to grow under these conditions
We observed that these GOF p53 sublines expressed a significantly low level of PSA in androgen-containing medium when compared with the parental LNCaP line and the P151S subline , suggesting that these p53 mutants repress AR activity

F.Horn (nucleardbcmbi.kun.nl), 21-Apr-2005