Multiple complementary transcripts of pCMa1, a novel gene located at chromosome 11p15.1-2, and melanocytic cell transformation.
The cDNA clone pCMa1 (0.45 kb) is one of the 12 novel cDNAs, previously identified when comparing RNA expression profiles of melanocytes, naevus cells, and non-metastatic melanoma cells. This clone did not reveal a unique long open reading frame. The pCMa1 gene localized to the distal, telomere proximal region on the short arm of chromosome 11.p15.1-2. Northern blot analyses with single-stranded cRNA probes revealed the presence of various complementary pCMa1 transcripts of different lengths, which are not enriched in the poly(A)(+) RNA fraction. The arbitrarily defined plus strand (used as a probe) mainly hybridized to 0.45 kb and 4.0 kb minus transcripts in total RNA samples, and the minus strand (used as a probe) hybridized to a major plus transcript of 4.0 kb. By RNA in situ hybridization, the highest levels of the plus transcripts were observed in melanocytic naevi (12/12), particularly in congenital naevi, whereas normal skin melanocytes (12/12) were negative. pCMa1 plus transcripts were detected in naevus cell nests (100%) near the dermo-epidermal junction. Expression, however, diminished to some extent in the deeper parts of the melanocytic naevi. Although most of the cutaneous primary melanoma lesions (11/15) showed detectable, but variable levels of plus transcripts of pCMa1 in the papillary to reticular dermis, not more than 10% of the melanoma cells were positive. The majority of melanoma metastases (6/7) were negative, while the positive lesion originated from a patient with a positive primary melanoma. Furthermore, plus transcripts were present in the nuclei of non-metastatic melanoma cells in culture, whereas metastatic cells showed elevated expression both in the nucleus and in the cytoplasm. Briefly, the data show transient up-regulation of pCMa1 in neoplastic progression of melanocytic cells, with peak levels occurring during naevus stages, and suggest that pCMa1 is a molecular marker in melanocytes for the early changes from the proliferating phenotype to malignant transformation.
Meije
Clifton B
CB
Department of Biochemistry, University of Nijmegen, The Netherlands.
Das
Pranab K
PK
Jans
Miranda M E
MM
Hau
Chi
C
van der Wal
Allard C
AC
Alders
Marielle
M
Hakvoort
Theodorus B M
TB
Weidle
Ulrich H
UH
Lamers
Wouter H
WH
Swart
Guido W M
GW
D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D018450:Disease Progression; D015723:Gene Library; D006801:Humans; D008544:Melanocytes / Q000473:pathology*; D008545:Melanoma / Q000235:genetics*; D009508:Nevus, Pigmented / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012334:RNA, Neoplasm / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D014158:Transcription, Genetic
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm