PMID- 11389049
OWN - NLM
STAT- MEDLINE
DCOM- 20010621
LR  - 20071114
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 61
IP  - 11
DP  - 2001 Jun 1
TI  - Progressive decreases in nuclear retinoid receptors during skin squamous 
      carcinogenesis.
PG  - 4306-10
AB  - Retinoids are essential for normal skin growth, differentiation, and apoptosis 
      and are active pharmacologically in the prevention and treatment of skin cancers 
      and other lesions. Retinoid effects are mediated mainly by retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs), which act as transcription 
      factors to alter gene expression. Using in situ hybridization, we analyzed the 
      expression of RARs and RXRs in normal sun-exposed skin (n = 85), squamous cell 
      carcinoma (SCC; n = 28), and actinic keratosis [AK (a precursor to SCC); n = 38]. 
      The expressions of five receptors (RAR-alpha and -gamma and RXR-alpha, -beta, and 
      -gamma) were moderate to very strong in normal skin, with higher expressions in 
      spinous and granular layers than in the basal layer. RAR-beta expression was weak 
      or absent in normal and lesion samples. All five receptors expressed in the skin 
      were suppressed progressively from normal skin to premalignant skin (AK) to 
      invasive skin SCC. Specific receptor decreases in lesions relative to normal skin 
      ranged from 75% (RXR-beta) to 96% (RAR-alpha) in SCC and from 37% (RAR-gamma) to 
      68% (RXR-beta) in AK. The degree of suppression of RXR-alpha and RAR-gamma, the 
      two predominant retinoid receptors in skin, was relatively less for RXR-alpha 
      (58% versus 86%; P = 0.015) and relatively greater for RAR-gamma (37% versus 89%; 
      P = 0.0001) between AK and SCC, suggesting that suppression of RXR-alpha may be 
      an earlier event and expression of RAR-gamma may be a later event of multistep 
      squamous skin carcinogenesis. Our results indicate that suppressed expression of 
      retinoid receptors occurs early (in AK) and is associated with progression of 
      squamous skin carcinogenesis to SCC.
FAU - Xu, X C
AU  - Xu XC
AD  - Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson 
      Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
FAU - Wong, W Y
AU  - Wong WY
FAU - Goldberg, L
AU  - Goldberg L
FAU - Baer, S C
AU  - Baer SC
FAU - Wolf, J E
AU  - Wolf JE
FAU - Ramsdell, W M
AU  - Ramsdell WM
FAU - Alberts, D S
AU  - Alberts DS
FAU - Lippman, S M
AU  - Lippman SM
FAU - Lotan, R
AU  - Lotan R
LA  - eng
GR  - 2P01 CA27502/CA/NCI NIH HHS/United States
GR  - 5P01 CA68233/CA/NCI NIH HHS/United States
GR  - CA16672/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Receptors, Retinoic Acid)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Basal Cell/metabolism
MH  - Carcinoma, Squamous Cell/*metabolism
MH  - Humans
MH  - In Situ Hybridization
MH  - Keratosis/metabolism
MH  - Middle Aged
MH  - Precancerous Conditions/metabolism
MH  - Receptors, Retinoic Acid/*biosynthesis/classification
MH  - Skin/*metabolism
MH  - Skin Neoplasms/*metabolism
EDAT- 2001/06/05 10:00
MHDA- 2001/06/22 10:01
CRDT- 2001/06/05 10:00
PHST- 2001/06/05 10:00 [pubmed]
PHST- 2001/06/22 10:01 [medline]
PHST- 2001/06/05 10:00 [entrez]
PST - ppublish
SO  - Cancer Res. 2001 Jun 1;61(11):4306-10.