Differential Expression Patterns of the Heterochromatin Proteins HP1α and HP1β in Different Tumor Types
A Contreras, MC Gutierrez, TK Hale. Baylor College of Medicine, Houston, TX; Massey University, Palmerston North, Manawatu-Wanganui, New Zealand
Background: Heterochromatin are condensed regions in the genome with repressed transcription. HP1α and HP1β are two heterochromatin associated proteins that have been shown to be lost in various tumors. We have previously shown that HP1β is significantly decreased in thyroid follicular, papillary, and anaplastic carcinomas when compared to normal. In order to extend these studies, we performed Western blot analysis on thyroid papillary carcinomas and IHC on a tissue microarray with different tumor types.
Design: Frozen matched thyroid normal and papillary carcinoma tissue from 4 patients was obtained from the Christchurch Cancer Society Tissue Bank. Total protein was isolated from these tissue samples, resolved by SDS-PAGE, then transferred to nitrocellulose. The blots were then incubated with either a HP1α or HP1β antibodies. A Tissue Microarray (TMA) with 6 brain, 8 colon, 10 lung, 5 cervical, 10 uterine, 8 bladder, 9 breast, 10 ovarian, 10 prostate, and 6 kidney tumors was created. IHC using antibodies against HP1α and HP1β was performed on this TMA, and the presence of these proteins was analyzed.
Results: As shown below, both HP1α and HP1β are downregulated in thyroid papillary carcinomas when compared to normal. Interestingly, both proteins were lost to a greater degree in the 3 out of 4 cases with metastatic tumor (cases 1, 3, and 4).
HP1α and HP1β were similarly expressed in the following tumors: brain, cervical, bladder, breast, ovarian, and prostate. In colon (7/8), lung (8/10), uterine (6/10), and kidney (6/6), HP1β is lost whereas HP1α expression is retained in a significant majority of these tumor types.
Conclusions: HP1α and HP1β is significantly decreased in thyroid papillary carcinoma when analyzed by Western blot. Thus, in thyroid carcinomas, loss of the HP1 proteins may result in altered gene expression that promotes tumorigenesis. A significant loss of these proteins may confer a metastatic advantage to this tumor type. Interestingly, the observation that HP1β is lost in a subset of tumors that retain HP1α expression may imply a different pathogenesis of these tumor types.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 223, Wednesday Morning