Limits...
Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.

Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B - Br. J. Cancer (2008)

Bottom Line: There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model.The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern.The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles (ULB), Campus Erasme, Route de Lennik 808, B 1070 Bruxelles, Belgique. lingjin@ulb.ac.be

ABSTRACT
Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

Show MeSH

Related in: MedlinePlus

Immunohistochemistry for Sodium Iodide Symporter (NIS), Thyroglobulin (Tg), Iodinated-thyroglobulin (Tg-I) and incorporation of iodide visualized by autoradiography (ARG). (A, F, K and P) 6-month C57Bl/6, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (B, G, L and Q) 6-month E7, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (C, H, M and R) 6-month RET/PTC3, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (D, L, N and S) 6-month RET/PTC3, disorganized papillary cyst region NIS, Tg, Tg-I immunostaining and autoradiography respectively; (E, J and O) 10-month RET/PTC3, solid mass region NIS, Tg, Tg-I immunostaining, respectively. Original magnification for (E, J and O): × 10, scale bar: 100 μm. Original magnification for other images: × 40; scale bar:30 μm. Inserts magnification: × 40.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2600679&req=5

fig3: Immunohistochemistry for Sodium Iodide Symporter (NIS), Thyroglobulin (Tg), Iodinated-thyroglobulin (Tg-I) and incorporation of iodide visualized by autoradiography (ARG). (A, F, K and P) 6-month C57Bl/6, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (B, G, L and Q) 6-month E7, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (C, H, M and R) 6-month RET/PTC3, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (D, L, N and S) 6-month RET/PTC3, disorganized papillary cyst region NIS, Tg, Tg-I immunostaining and autoradiography respectively; (E, J and O) 10-month RET/PTC3, solid mass region NIS, Tg, Tg-I immunostaining, respectively. Original magnification for (E, J and O): × 10, scale bar: 100 μm. Original magnification for other images: × 40; scale bar:30 μm. Inserts magnification: × 40.

Mentions: E7 thyroids were much larger than WT thyroids at all ages (Figure 1D–F). At 2, 6, and 10 months, the follicular cells, with a not well marked cellular border, were crowded and overlapping all around the follicles, with a 1.9-fold cell number increase at 2 months in comparison with the WT (Figure 2A and D). The nuclei were hyperchromatic with an increase in the nuclear/cytoplasmic ratio (Figure 2D), The follicular border appeared ‘palissade like' (Figure 2D–F). At 6 and 10 months huge follicles lined with flat follicular cells (Figures 2E, F, 3B and Q) coexisted with small round and irregularly shaped follicles with ‘palissade like' borders (Figures 2E, F, 3B and Q).


Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.

Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B - Br. J. Cancer (2008)

Immunohistochemistry for Sodium Iodide Symporter (NIS), Thyroglobulin (Tg), Iodinated-thyroglobulin (Tg-I) and incorporation of iodide visualized by autoradiography (ARG). (A, F, K and P) 6-month C57Bl/6, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (B, G, L and Q) 6-month E7, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (C, H, M and R) 6-month RET/PTC3, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (D, L, N and S) 6-month RET/PTC3, disorganized papillary cyst region NIS, Tg, Tg-I immunostaining and autoradiography respectively; (E, J and O) 10-month RET/PTC3, solid mass region NIS, Tg, Tg-I immunostaining, respectively. Original magnification for (E, J and O): × 10, scale bar: 100 μm. Original magnification for other images: × 40; scale bar:30 μm. Inserts magnification: × 40.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2600679&req=5

fig3: Immunohistochemistry for Sodium Iodide Symporter (NIS), Thyroglobulin (Tg), Iodinated-thyroglobulin (Tg-I) and incorporation of iodide visualized by autoradiography (ARG). (A, F, K and P) 6-month C57Bl/6, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (B, G, L and Q) 6-month E7, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (C, H, M and R) 6-month RET/PTC3, NIS, Tg, Tg-I immunostaining and autoradiography, respectively; (D, L, N and S) 6-month RET/PTC3, disorganized papillary cyst region NIS, Tg, Tg-I immunostaining and autoradiography respectively; (E, J and O) 10-month RET/PTC3, solid mass region NIS, Tg, Tg-I immunostaining, respectively. Original magnification for (E, J and O): × 10, scale bar: 100 μm. Original magnification for other images: × 40; scale bar:30 μm. Inserts magnification: × 40.
Mentions: E7 thyroids were much larger than WT thyroids at all ages (Figure 1D–F). At 2, 6, and 10 months, the follicular cells, with a not well marked cellular border, were crowded and overlapping all around the follicles, with a 1.9-fold cell number increase at 2 months in comparison with the WT (Figure 2A and D). The nuclei were hyperchromatic with an increase in the nuclear/cytoplasmic ratio (Figure 2D), The follicular border appeared ‘palissade like' (Figure 2D–F). At 6 and 10 months huge follicles lined with flat follicular cells (Figures 2E, F, 3B and Q) coexisted with small round and irregularly shaped follicles with ‘palissade like' borders (Figures 2E, F, 3B and Q).

Bottom Line: There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model.The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern.The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC.

View Article: PubMed Central - PubMed

Affiliation: Institut de Recherche Interdisciplinaire (IRIBHM), Faculté de Médecine, Université Libre de Bruxelles (ULB), Campus Erasme, Route de Lennik 808, B 1070 Bruxelles, Belgique. lingjin@ulb.ac.be

ABSTRACT
Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.

Show MeSH
Related in: MedlinePlus